17-61680480-C-CTTTCT

Position:

• chr17-61680480-C-CTTTCT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_032043.3(BRIP1):​c.*2815_*2816insAGAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0052 (23 hom., cov: 0)
• Consequence: BRIP1 NM_032043.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.0550

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00517 (642/124070) while in subpopulation AFR AF= 0.0168 (532/31740). AF 95% confidence interval is 0.0156. There are 23 homozygotes in gnomad4. There are 315 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 23 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRIP1	NM_032043.3	c.*2815_*2816insAGAAA		3_prime_UTR_variant	20/20	ENST00000259008.7	NP_114432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRIP1	ENST00000259008.7	c.*2815_*2816insAGAAA		3_prime_UTR_variant	20/20	1	NM_032043.3	ENSP00000259008	P2
BRIP1	ENST00000682755.1	c.*2815_*2816insAGAAA		3_prime_UTR_variant	18/18			ENSP00000507660

Frequencies

GnomAD3 genomes AF: 0.00515 AC: 639 AN: 124094 Hom.: 23 Cov.: 0

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00580

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000482

Gnomad SAS AF: 0.000504

Gnomad FIN AF: 0.000935

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.000357

Gnomad OTH AF: 0.00676

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

GnomAD4 genome AF: 0.00517 AC: 642 AN: 124070 Hom.: 23 Cov.: 0 AF XY: 0.00538 AC XY: 315 AN XY: 58552

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.00580

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000484

Gnomad4 SAS AF: 0.000507

Gnomad4 FIN AF: 0.000935

Gnomad4 NFE AF: 0.000357

Gnomad4 OTH AF: 0.00677

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Fanconi anemia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Breast neoplasm Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555571892; hg19: chr17-59757841;