rs4988351

Variant names:

• chr17-61780448-C-G
• rs4988351
• NM_032043.3:c.1795-47G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-61780448-C-G
• chr17-61780448-C-A
• chr17-61780448-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032043.3(BRIP1):​c.1795-47G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,550,092 control chromosomes in the GnomAD database, including 438,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46475 hom., cov: 31)
  • Exomes 𝑓: 0.75 (391843 hom.)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.152
• 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: Illumina, Orphanet
• Fanconi anemia complementation group J

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

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

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-61780448-C-G is Benign according to our data. Variant chr17-61780448-C-G is described in ClinVar as Benign. ClinVar VariationId is 262005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRIP1	NM_032043.3	MANE Select	c.1795-47G>C		intron	N/A	NP_114432.2	Q9BX63-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRIP1	ENST00000259008.7	TSL:1 MANE Select	c.1795-47G>C		intron	N/A	ENSP00000259008.2	Q9BX63-1
	BRIP1	ENST00000682453.1		c.1795-47G>C		intron	N/A	ENSP00000506943.1	Q9BX63-1
	BRIP1	ENST00000683039.1		c.1795-47G>C		intron	N/A	ENSP00000508303.1	Q9BX63-1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118178 AN: 151952 Hom.: 46452 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.763

GnomAD2 exomes AF: 0.737 AC: 182419 AN: 247544 AF XY: 0.746

Gnomad AFR exome AF: 0.856

Gnomad AMR exome AF: 0.496

Gnomad ASJ exome AF: 0.744

Gnomad EAS exome AF: 0.829

Gnomad FIN exome AF: 0.804

Gnomad NFE exome AF: 0.751

Gnomad OTH exome AF: 0.738

GnomAD4 exome AF: 0.746 AC: 1043578 AN: 1398022 Hom.: 391843 Cov.: 23 AF XY: 0.749 AC XY: 523283 AN XY: 698728

African (AFR) AF: 0.861 AC: 27564 AN: 32022

American (AMR) AF: 0.511 AC: 22740 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 19211 AN: 25754

East Asian (EAS) AF: 0.787 AC: 30906 AN: 39250

South Asian (SAS) AF: 0.794 AC: 67059 AN: 84406

European-Finnish (FIN) AF: 0.801 AC: 42447 AN: 52964

Middle Eastern (MID) AF: 0.770 AC: 3479 AN: 4516

European-Non Finnish (NFE) AF: 0.744 AC: 785847 AN: 1056410

Other (OTH) AF: 0.761 AC: 44325 AN: 58216

GnomAD4 genome AF: 0.778 AC: 118246 AN: 152070 Hom.: 46475 Cov.: 31 AF XY: 0.777 AC XY: 57771 AN XY: 74346

African (AFR) AF: 0.853 AC: 35393 AN: 41476

American (AMR) AF: 0.632 AC: 9654 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2497 AN: 3470

East Asian (EAS) AF: 0.821 AC: 4245 AN: 5172

South Asian (SAS) AF: 0.795 AC: 3835 AN: 4822

European-Finnish (FIN) AF: 0.810 AC: 8559 AN: 10570

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

European-Non Finnish (NFE) AF: 0.756 AC: 51408 AN: 67974

Other (OTH) AF: 0.765 AC: 1613 AN: 2108

Alfa AF: 0.764 Hom.: 7904

Bravo AF: 0.764

Asia WGS AF: 0.803 AC: 2793 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.9
DANN	Benign	0.89
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4988351; hg19: chr17-59857809; COSMIC: COSV51993354; COSMIC: COSV51993354;