17-61680480-C-CTTTCTT

Variant names:

• chr17-61680480-C-CTTTCTT
• rs1555571892
• NM_032043.3:c.*2815_*2816insAAGAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_032043.3(BRIP1):​c.*2815_*2816insAAGAAA 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 0.24 (4484 hom., cov: 0)
• Consequence: BRIP1 NM_032043.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• 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, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• colorectal adenoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

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_*2816insAAGAAA		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_*2816insAAGAAA		3_prime_UTR	Exon 20 of 20	ENSP00000259008.2	Q9BX63-1
	BRIP1	ENST00000682755.1		c.*2815_*2816insAAGAAA		3_prime_UTR	Exon 18 of 18	ENSP00000507660.1	A0A804HJV4

Frequencies

GnomAD3 genomes AF: 0.241 AC: 29789 AN: 123850 Hom.: 4480 Cov.: 0

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0924

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.241 AC: 29785 AN: 123824 Hom.: 4484 Cov.: 0 AF XY: 0.241 AC XY: 14081 AN XY: 58426

African (AFR) AF: 0.203 AC: 6422 AN: 31672

American (AMR) AF: 0.444 AC: 5036 AN: 11336

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 896 AN: 3224

East Asian (EAS) AF: 0.227 AC: 940 AN: 4132

South Asian (SAS) AF: 0.191 AC: 752 AN: 3936

European-Finnish (FIN) AF: 0.154 AC: 822 AN: 5340

Middle Eastern (MID) AF: 0.180 AC: 36 AN: 200

European-Non Finnish (NFE) AF: 0.234 AC: 14379 AN: 61524

Other (OTH) AF: 0.262 AC: 424 AN: 1616

Alfa AF: 0.0457 Hom.: 66

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Breast neoplasm (1)
-	1	-	Fanconi anemia (1)
-	1	-	not specified (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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1555571892;

hg19: chr17-59757841;