rs16945628

Variant names:

• chr17-61789868-T-C
• rs16945628
• NM_032043.3:c.1473+3729A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032043.3(BRIP1):​c.1473+3729A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,518 control chromosomes in the GnomAD database, including 28,183 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (28183 hom., cov: 32)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 19 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032043.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRIP1	NM_032043.3	MANE Select	c.1473+3729A>G		intron	N/A	NP_114432.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRIP1	ENST00000259008.7	TSL:1 MANE Select	c.1473+3729A>G		intron	N/A	ENSP00000259008.2
	BRIP1	ENST00000682453.1		c.1473+3729A>G		intron	N/A	ENSP00000506943.1
	BRIP1	ENST00000683039.1		c.1473+3729A>G		intron	N/A	ENSP00000508303.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 90819 AN: 151402 Hom.: 28192 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.599 AC: 90834 AN: 151518 Hom.: 28183 Cov.: 32 AF XY: 0.598 AC XY: 44310 AN XY: 74080

African (AFR) AF: 0.449 AC: 18358 AN: 40924

American (AMR) AF: 0.513 AC: 7830 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2174 AN: 3466

East Asian (EAS) AF: 0.621 AC: 3218 AN: 5182

South Asian (SAS) AF: 0.552 AC: 2662 AN: 4822

European-Finnish (FIN) AF: 0.745 AC: 7877 AN: 10574

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46574 AN: 67976

Other (OTH) AF: 0.602 AC: 1270 AN: 2110

Alfa AF: 0.647 Hom.: 118718

Bravo AF: 0.572

Asia WGS AF: 0.554 AC: 1926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.90
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16945628; hg19: chr17-59867229;