GeneBe

chr17-43104104-GA-G

Position:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_007294.4(BRCA1):​c.441+17delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000506 in 1,561,140 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

BRCA1
NM_007294.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.296
Variant links:
Genes affected
BRCA1 (HGNC:1100): (BRCA1 DNA repair associated) This gene encodes a 190 kD nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The BRCA1 gene contains 22 exons spanning about 110 kb of DNA. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2020]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP6
Variant 17-43104104-GA-G is Benign according to our data. Variant chr17-43104104-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 462647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BRCA1NM_007294.4 linkuse as main transcriptc.441+17delT intron_variant ENST00000357654.9 NP_009225.1 P38398-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BRCA1ENST00000357654.9 linkuse as main transcriptc.441+17delT intron_variant 1 NM_007294.4 ENSP00000350283.3 P38398-1

Frequencies

GnomAD3 genomes
AF:
0.000318
AC:
46
AN:
144688
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00111
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000153
Gnomad OTH
AF:
0.000500
GnomAD4 exome
AF:
0.0000233
AC:
33
AN:
1416350
Hom.:
0
Cov.:
33
AF XY:
0.0000170
AC XY:
12
AN XY:
706172
show subpopulations
Gnomad4 AFR exome
AF:
0.000891
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.30e-7
Gnomad4 OTH exome
AF:
0.0000512
GnomAD4 genome
AF:
0.000318
AC:
46
AN:
144790
Hom.:
0
Cov.:
32
AF XY:
0.000255
AC XY:
18
AN XY:
70496
show subpopulations
Gnomad4 AFR
AF:
0.00110
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000153
Gnomad4 OTH
AF:
0.000496

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingColor Diagnostics, LLC DBA Color HealthJul 17, 2015- -
Familial cancer of breast Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 11, 2013The variant is found in HEREDICANCER,BR-OV-HEREDIC panel(s). -
Hereditary breast ovarian cancer syndrome Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 11, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs730881449; hg19: chr17-41256121; API