17-61822429-G-T

Variant names:

• chr17-61822429-G-T
• rs6504074
• NM_032043.3:c.628-13672C>A

Variant summary

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

The NM_032043.3(BRIP1):​c.628-13672C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 151,932 control chromosomes in the GnomAD database, including 10,702 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 0.35 (10702 hom., cov: 31)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 14 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 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.628-13672C>A		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.628-13672C>A		intron	N/A	ENSP00000259008.2
	BRIP1	ENST00000682453.1		c.628-13672C>A		intron	N/A	ENSP00000506943.1
	BRIP1	ENST00000683039.1		c.628-13672C>A		intron	N/A	ENSP00000508303.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53773 AN: 151814 Hom.: 10679 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.354 AC: 53849 AN: 151932 Hom.: 10702 Cov.: 31 AF XY: 0.358 AC XY: 26552 AN XY: 74244

African (AFR) AF: 0.531 AC: 21984 AN: 41412

American (AMR) AF: 0.394 AC: 6012 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1246 AN: 5168

South Asian (SAS) AF: 0.470 AC: 2264 AN: 4822

European-Finnish (FIN) AF: 0.239 AC: 2512 AN: 10530

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17767 AN: 67964

Other (OTH) AF: 0.336 AC: 709 AN: 2108

Alfa AF: 0.267 Hom.: 2968

Bravo AF: 0.369

Asia WGS AF: 0.361 AC: 1255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.41
PhyloP100		0.075
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: rs6504074; hg19: chr17-59899790;