rs1557720

Variant names:

• chr17-61709013-T-A
• rs1557720
• NM_032043.3:c.2492+6938A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-61709013-T-A
• chr17-61709013-T-C
• chr17-61709013-T-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.2492+6938A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,952 control chromosomes in the GnomAD database, including 28,845 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 0.61 (28845 hom., cov: 31)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 10 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.2492+6938A>T		intron_variant	Intron 17 of 19	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.2492+6938A>T		intron_variant	Intron 17 of 19	1	NM_032043.3	ENSP00000259008.2

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92490 AN: 151834 Hom.: 28806 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.609 AC: 92590 AN: 151952 Hom.: 28845 Cov.: 31 AF XY: 0.604 AC XY: 44843 AN XY: 74262

African (AFR) AF: 0.668 AC: 27701 AN: 41470

American (AMR) AF: 0.737 AC: 11250 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2035 AN: 3468

East Asian (EAS) AF: 0.722 AC: 3728 AN: 5162

South Asian (SAS) AF: 0.458 AC: 2202 AN: 4804

European-Finnish (FIN) AF: 0.407 AC: 4292 AN: 10536

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39519 AN: 67926

Other (OTH) AF: 0.629 AC: 1332 AN: 2116

Alfa AF: 0.423 Hom.: 1011

Bravo AF: 0.640

Asia WGS AF: 0.536 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.89
PhyloP100		-0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs1557720; hg19: chr17-59786374;