Is BRCA1 c.4675+693del pathogenic?

BRCA1 c.4675+693del is classified Benign in BRCA1 (ClinVar, Expert panel, 1 submitter; last evaluated 2015-01-12). Common (popmax 14.9%, sas) — too common for a highly-penetrant pathogenic allele; Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 c.4675+693del?

BRCA1 c.4675+693del is associated with breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

BRCA1 c.4675+693del

Q: How common is BRCA1 c.4675+693del in the general population?

BRCA1 c.4675+693del is common (popmax 14.9%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs5820482 · VCV209365

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 14.9%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

breast-ovarian cancer, familial, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +693	deep intronic (+693 nt into the intron)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.21	GERP -1.3
Overall
CADD	2.756	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.9% South Asian · 718/4,808 alleles

Filtering AF 14% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.7%

Overall 8.42% 12,797/152,018 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	14.9%	7
Ashkenazi Jewishnot grpmax-eligible	14.7%	7
Middle Eastern	13.6%	7
European (non-Finnish)	12.1%	8
Finnishnot grpmax-eligible	10.5%	10
Remaining individualsnot grpmax-eligible	8.63%	12
Amishnot grpmax-eligible	7.58%	13
Admixed American	6.69%	15
African / African-American	2.22%	45
East Asian	0.116%	865

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BRCA1
Coding: c.4675+693del
MANE Select: NM_007294
dbSNP: rs5820482
Type: Deletion
Location: chr17:43073638 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB

Full BRCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

breast-ovarian cancer, familial, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

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BRCA1 c.442-22_442-13del Pathogenic ★★★ same condition
BRCA1 c.4484+1del Pathogenic ★★★ same condition
BRCA1 c.5277+1_5277+6del Pathogenic ★★★ same condition
BRCA1 c.5278-2del Pathogenic ★★★ same condition
BRCA1 c.5333-36_5406+400del Pathogenic ★★★ same condition
BRCA1 c.5470_5477del Pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/brca1-c-4675-plus-693del (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown