NM_032043.3:c.*2815_*2816insAAAAGAAA

Variant names:

• chr17-61680480-C-CTTTCTTTT
• rs1555571892
• NM_032043.3:c.*2815_*2816insAAAAGAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_032043.3(BRIP1):​c.*2815_*2816insAAAAGAAA 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 0.012 (46 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0122 (1517/124002) while in subpopulation SAS AF = 0.0322 (127/3942). AF 95% confidence interval is 0.0277. There are 46 homozygotes in GnomAd4. There are 731 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 46 AD,AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1521 AN: 124026 Hom.: 47 Cov.: 0

Gnomad AFR AF: 0.00363

Gnomad AMI AF: 0.0500

Gnomad AMR AF: 0.00906

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.00991

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0157

Gnomad OTH AF: 0.00800

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

GnomAD4 genome AF: 0.0122 AC: 1517 AN: 124002 Hom.: 46 Cov.: 0 AF XY: 0.0125 AC XY: 731 AN XY: 58524

African (AFR) AF: 0.00363 AC: 115 AN: 31724

American (AMR) AF: 0.00906 AC: 103 AN: 11372

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 44 AN: 3230

East Asian (EAS) AF: 0.0138 AC: 57 AN: 4134

South Asian (SAS) AF: 0.0322 AC: 127 AN: 3942

European-Finnish (FIN) AF: 0.00991 AC: 53 AN: 5346

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

European-Non Finnish (NFE) AF: 0.0156 AC: 963 AN: 61590

Other (OTH) AF: 0.00800 AC: 13 AN: 1624

Alfa AF: 0.00598 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;