rs60657820

Variant names:

• chr17-61681206-C-G
• rs60657820
• NM_032043.3:c.*2090G>C

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.*2090G>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 0.372 in 199,364 control chromosomes in the GnomAD database, including 14,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11484 hom., cov: 31)
  • Exomes 𝑓: 0.35 (2976 hom.)
• Consequence: BRIP1 NM_032043.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.505
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 17-61681206-C-G is Benign according to our data. Variant chr17-61681206-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 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.*2090G>C		3_prime_UTR	Exon 20 of 20	NP_114432.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRIP1	ENST00000259008.7	TSL:1 MANE Select	c.*2090G>C		3_prime_UTR	Exon 20 of 20	ENSP00000259008.2
	BRIP1	ENST00000682755.1		c.*2090G>C		3_prime_UTR	Exon 18 of 18	ENSP00000507660.1
	BRIP1	ENST00000682453.1		c.*2090G>C		downstream_gene	N/A	ENSP00000506943.1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57556 AN: 151414 Hom.: 11465 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.378

GnomAD4 exome AF: 0.347 AC: 16615 AN: 47830 Hom.: 2976 AF XY: 0.346 AC XY: 7671 AN XY: 22152

African (AFR) AF: 0.477 AC: 933 AN: 1958

American (AMR) AF: 0.257 AC: 367 AN: 1430

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 955 AN: 3198

East Asian (EAS) AF: 0.427 AC: 3222 AN: 7554

South Asian (SAS) AF: 0.232 AC: 92 AN: 396

European-Finnish (FIN) AF: 0.206 AC: 7 AN: 34

Middle Eastern (MID) AF: 0.366 AC: 104 AN: 284

European-Non Finnish (NFE) AF: 0.331 AC: 9611 AN: 29022

Other (OTH) AF: 0.335 AC: 1324 AN: 3954

GnomAD4 genome AF: 0.380 AC: 57628 AN: 151534 Hom.: 11484 Cov.: 31 AF XY: 0.373 AC XY: 27611 AN XY: 74068

African (AFR) AF: 0.505 AC: 20832 AN: 41268

American (AMR) AF: 0.315 AC: 4800 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1056 AN: 3466

East Asian (EAS) AF: 0.485 AC: 2473 AN: 5094

South Asian (SAS) AF: 0.263 AC: 1267 AN: 4818

European-Finnish (FIN) AF: 0.242 AC: 2559 AN: 10558

Middle Eastern (MID) AF: 0.469 AC: 135 AN: 288

European-Non Finnish (NFE) AF: 0.346 AC: 23457 AN: 67796

Other (OTH) AF: 0.381 AC: 801 AN: 2102

Alfa AF: 0.217 Hom.: 442

Bravo AF: 0.394

Asia WGS AF: 0.343 AC: 1191 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.39
PhyloP100		-0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs60657820; hg19: chr17-59758567;