rs1978111

Variant names:

• chr17-61683138-A-G
• rs1978111
• NM_032043.3:c.*158T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-61683138-A-G
• chr17-61683138-A-C
• chr17-61683138-A-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.*158T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 929,366 control chromosomes in the GnomAD database, including 170,514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28545 hom., cov: 31)
  • Exomes 𝑓: 0.59 (141969 hom.)
• Consequence: BRIP1 NM_032043.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.426
• Publications: 8 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=-0.84).
• BP6: Variant 17-61683138-A-G is Benign according to our data. Variant chr17-61683138-A-G is described in ClinVar as Benign. ClinVar VariationId is 324344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.723 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.*158T>C		3_prime_UTR	Exon 20 of 20	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.*158T>C		3_prime_UTR	Exon 20 of 20	ENSP00000259008.2	Q9BX63-1
	BRIP1	ENST00000682453.1		c.*158T>C		3_prime_UTR	Exon 21 of 21	ENSP00000506943.1	Q9BX63-1
	BRIP1	ENST00000683039.1		c.*158T>C		3_prime_UTR	Exon 21 of 21	ENSP00000508303.1	Q9BX63-1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92015 AN: 151786 Hom.: 28511 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.592 AC: 460403 AN: 777464 Hom.: 141969 Cov.: 10 AF XY: 0.587 AC XY: 232385 AN XY: 395888

African (AFR) AF: 0.662 AC: 12012 AN: 18154

American (AMR) AF: 0.767 AC: 14659 AN: 19100

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 8999 AN: 15752

East Asian (EAS) AF: 0.748 AC: 23832 AN: 31864

South Asian (SAS) AF: 0.459 AC: 23752 AN: 51706

European-Finnish (FIN) AF: 0.438 AC: 12804 AN: 29246

Middle Eastern (MID) AF: 0.647 AC: 1641 AN: 2536

European-Non Finnish (NFE) AF: 0.596 AC: 341238 AN: 572888

Other (OTH) AF: 0.593 AC: 21466 AN: 36218

GnomAD4 genome AF: 0.606 AC: 92110 AN: 151902 Hom.: 28545 Cov.: 31 AF XY: 0.601 AC XY: 44628 AN XY: 74262

African (AFR) AF: 0.656 AC: 27148 AN: 41406

American (AMR) AF: 0.734 AC: 11221 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2034 AN: 3470

East Asian (EAS) AF: 0.721 AC: 3732 AN: 5176

South Asian (SAS) AF: 0.460 AC: 2205 AN: 4796

European-Finnish (FIN) AF: 0.408 AC: 4293 AN: 10518

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

European-Non Finnish (NFE) AF: 0.583 AC: 39616 AN: 67940

Other (OTH) AF: 0.630 AC: 1331 AN: 2114

Alfa AF: 0.470 Hom.: 1420

Bravo AF: 0.636

Asia WGS AF: 0.534 AC: 1858 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Fanconi anemia complementation group J (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.49
DANN	Benign	0.56
PhyloP100		0.43
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: rs1978111; hg19: chr17-59760499;