rs1978244

Variant names:

• chr17-61798564-G-A
• rs1978244
• NM_032043.3:c.1340+536C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-61798564-G-A
• chr17-61798564-G-C
• chr17-61798564-G-T

Variant summary

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

The NM_032043.3(BRIP1):​c.1340+536C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 151,892 control chromosomes in the GnomAD database, including 46,739 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 0.78 (46739 hom., cov: 30)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.1340+536C>T		intron_variant	Intron 9 of 19	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.1340+536C>T		intron_variant	Intron 9 of 19	1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118442 AN: 151774 Hom.: 46719 Cov.: 30

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.780 AC: 118506 AN: 151892 Hom.: 46739 Cov.: 30 AF XY: 0.780 AC XY: 57939 AN XY: 74254

African (AFR) AF: 0.851 AC: 35304 AN: 41466

American (AMR) AF: 0.634 AC: 9660 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2496 AN: 3466

East Asian (EAS) AF: 0.822 AC: 4264 AN: 5186

South Asian (SAS) AF: 0.797 AC: 3833 AN: 4812

European-Finnish (FIN) AF: 0.829 AC: 8764 AN: 10574

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51527 AN: 67846

Other (OTH) AF: 0.769 AC: 1621 AN: 2108

Alfa AF: 0.752 Hom.: 18137

Bravo AF: 0.765

Asia WGS AF: 0.805 AC: 2777 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.57
PhyloP100		-2.1
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: rs1978244; hg19: chr17-59875925;