NM_032043.3:c.*3489T>C

Variant names:

• chr17-61679807-A-G
• rs140891191
• NM_032043.3:c.*3489T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_032043.3(BRIP1):​c.*3489T>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 0.00552 in 152,300 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: 𝑓 0.0055 (8 hom., cov: 32)
• Consequence: BRIP1 NM_032043.3 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.511
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-61679807-A-G is Benign according to our data. Variant chr17-61679807-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 324293.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00552 (840/152300) while in subpopulation NFE AF = 0.00963 (655/68038). AF 95% confidence interval is 0.00902. There are 8 homozygotes in GnomAd4. There are 393 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AD,AR gene

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.*3489T>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.*3489T>C		3_prime_UTR	Exon 20 of 20	ENSP00000259008.2	Q9BX63-1
	BRIP1	ENST00000682755.1		c.*3489T>C		3_prime_UTR	Exon 18 of 18	ENSP00000507660.1	A0A804HJV4

Frequencies

GnomAD3 genomes AF: 0.00551 AC: 839 AN: 152182 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00208

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00767

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00963

Gnomad OTH AF: 0.00191

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

GnomAD4 genome AF: 0.00552 AC: 840 AN: 152300 Hom.: 8 Cov.: 32 AF XY: 0.00528 AC XY: 393 AN XY: 74476

African (AFR) AF: 0.00207 AC: 86 AN: 41554

American (AMR) AF: 0.00124 AC: 19 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00789 AC: 38 AN: 4818

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00963 AC: 655 AN: 68038

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00662 Hom.: 0

Bravo AF: 0.00529

Asia WGS AF: 0.00116 AC: 4 AN: 3474

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.6
DANN	Benign	0.85
PhyloP100		0.51

Splicing

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

Other links and lift over

dbSNP: rs140891191; hg19: chr17-59757168;