rs1555571892

Variant names:

• chr17-61680480-C-CTTTCT
• rs1555571892
• NM_032043.3:c.*2815_*2816insAGAAA

Your query was ambiguous. Multiple possible variants found:

• chr17-61680480-C-CTTTCT
• chr17-61680480-C-CTTTCTT
• chr17-61680480-C-CTTTCTTT
• chr17-61680480-C-CTTTCTTTT
• chr17-61680480-C-CTTTCTTTTT
• chr17-61680480-C-CTTTCTTTTTT
• chr17-61680480-C-CTTTCTTTTTTT
• chr17-61680480-C-CTTTCTTTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -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
• 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: ClinGen, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• colorectal adenoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 23 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.*2815_*2816insAGAAA		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.*2815_*2816insAGAAA		3_prime_UTR	Exon 20 of 20	ENSP00000259008.2	Q9BX63-1
	BRIP1	ENST00000682755.1		c.*2815_*2816insAGAAA		3_prime_UTR	Exon 18 of 18	ENSP00000507660.1	A0A804HJV4

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

African (AFR) AF: 0.0168 AC: 532 AN: 31740

American (AMR) AF: 0.00580 AC: 66 AN: 11378

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

East Asian (EAS) AF: 0.000484 AC: 2 AN: 4134

South Asian (SAS) AF: 0.000507 AC: 2 AN: 3944

European-Finnish (FIN) AF: 0.000935 AC: 5 AN: 5350

Middle Eastern (MID) AF: 0.0100 AC: 2 AN: 200

European-Non Finnish (NFE) AF: 0.000357 AC: 22 AN: 61624

Other (OTH) AF: 0.00677 AC: 11 AN: 1626

Alfa AF: 0.00 Hom.: 66

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Breast neoplasm (1)
-	1	-	Fanconi anemia (1)

Computational scores

Source: dbNSFP v4.9

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;