rs9897928

Variant names:

• chr17-61766669-A-T
• rs9897928
• NM_032043.3:c.2097+9732T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032043.3(BRIP1):​c.2097+9732T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,030 control chromosomes in the GnomAD database, including 47,281 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (47281 hom., cov: 31)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584
• Publications: 5 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: Illumina, Orphanet
• Fanconi anemia complementation group J

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hereditary breast carcinoma

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

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 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.2097+9732T>A		intron	N/A	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.2097+9732T>A		intron	N/A	ENSP00000259008.2	Q9BX63-1
	BRIP1	ENST00000682453.1		c.2097+9732T>A		intron	N/A	ENSP00000506943.1	Q9BX63-1
	BRIP1	ENST00000683039.1		c.2097+9732T>A		intron	N/A	ENSP00000508303.1	Q9BX63-1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119128 AN: 151912 Hom.: 47258 Cov.: 31

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.784 AC: 119196 AN: 152030 Hom.: 47281 Cov.: 31 AF XY: 0.784 AC XY: 58301 AN XY: 74318

African (AFR) AF: 0.865 AC: 35903 AN: 41488

American (AMR) AF: 0.638 AC: 9726 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2489 AN: 3468

East Asian (EAS) AF: 0.821 AC: 4248 AN: 5176

South Asian (SAS) AF: 0.796 AC: 3834 AN: 4816

European-Finnish (FIN) AF: 0.834 AC: 8810 AN: 10562

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51527 AN: 67964

Other (OTH) AF: 0.768 AC: 1621 AN: 2112

Alfa AF: 0.779 Hom.: 5792

Bravo AF: 0.769

Asia WGS AF: 0.803 AC: 2787 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9897928; hg19: chr17-59844030;