NM_032043.3:c.1935+11G>T

Variant names:

• chr17-61780250-C-A
• rs79121306
• NM_032043.3:c.1935+11G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_032043.3(BRIP1):​c.1935+11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000045 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.61
• Publications: 0 publications found

Genes affected

BRIP1 (HGNC:20473): (BRCA1 interacting helicase 1) The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations. [provided by RefSeq, Jul 2008]

BRIP1 Gene-Disease associations (from GenCC):

• familial ovarian cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Fanconi anemia

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Illumina
• Fanconi anemia complementation group J

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary breast carcinoma

  Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• colorectal adenoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-61780250-C-A is Benign according to our data. Variant chr17-61780250-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 506481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.1935+11G>T		intron_variant	Intron 13 of 19	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.1935+11G>T		intron_variant	Intron 13 of 19	1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149774 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000503 AC: 12 AN: 238708 AF XY: 0.0000700

Gnomad AFR exome AF: 0.0000637

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000457

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000454 AC: 65 AN: 1430952 Hom.: 0 Cov.: 34 AF XY: 0.0000492 AC XY: 35 AN XY: 711132

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000932 AC: 3 AN: 32180

American (AMR) AF: 0.0000472 AC: 2 AN: 42354

Ashkenazi Jewish (ASJ) AF: 0.0000392 AC: 1 AN: 25490

East Asian (EAS) AF: 0.00 AC: 0 AN: 38976

South Asian (SAS) AF: 0.000332 AC: 27 AN: 81204

European-Finnish (FIN) AF: 0.0000193 AC: 1 AN: 51760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4956

European-Non Finnish (NFE) AF: 0.0000274 AC: 30 AN: 1094984

Other (OTH) AF: 0.0000169 AC: 1 AN: 59048

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 149774 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73084

African (AFR) AF: 0.00 AC: 0 AN: 40724

American (AMR) AF: 0.00 AC: 0 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67428

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 24, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Familial cancer of breast;C1836860:Fanconi anemia complementation group J Benign:1

Jul 01, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.33
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs79121306; hg19: chr17-59857611;