chr17-61680480-C-CTTTCTTTTT

Variant names:

• chr17-61680480-C-CTTTCTTTTT
• rs1555571892
• NM_032043.3:c.*2815_*2816insAAAAAGAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_032043.3(BRIP1):​c.*2815_*2816insAAAAAGAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00024 (3 hom., cov: 0)
• Consequence: BRIP1 NM_032043.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.*2815_*2816insAAAAAGAAA		3_prime_UTR_variant	Exon 20 of 20	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.*2815_*2816insAAAAAGAAA		3_prime_UTR_variant	Exon 20 of 20	1	NM_032043.3	ENSP00000259008.2
BRIP1	ENST00000682755.1	c.*2815_*2816insAAAAAGAAA		3_prime_UTR_variant	Exon 18 of 18			ENSP00000507660.1

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 31 AN: 124094 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.000126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00120

Gnomad SAS AF: 0.00151

Gnomad FIN AF: 0.000374

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000227

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000242 AC: 30 AN: 124070 Hom.: 3 Cov.: 0 AF XY: 0.000256 AC XY: 15 AN XY: 58554

African (AFR) AF: 0.000126 AC: 4 AN: 31738

American (AMR) AF: 0.00 AC: 0 AN: 11378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3230

East Asian (EAS) AF: 0.00121 AC: 5 AN: 4138

South Asian (SAS) AF: 0.00127 AC: 5 AN: 3944

European-Finnish (FIN) AF: 0.000374 AC: 2 AN: 5350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 200

European-Non Finnish (NFE) AF: 0.000227 AC: 14 AN: 61622

Other (OTH) AF: 0.00 AC: 0 AN: 1626

Alfa AF: 0.00 Hom.: 66

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.055

Splicing

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

Other links and lift over

dbSNP: rs1555571892; hg19: chr17-59757841;