rs2378908

Variant names:

• chr17-61834404-G-A
• rs2378908
• NM_032043.3:c.627+12697C>T

Variant summary

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

The NM_032043.3(BRIP1):​c.627+12697C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,952 control chromosomes in the GnomAD database, including 2,200 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 0.15 (2200 hom., cov: 31)
• Consequence: BRIP1 NM_032043.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 13 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 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.627+12697C>T		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.627+12697C>T		intron	N/A	ENSP00000259008.2	Q9BX63-1
	BRIP1	ENST00000682453.1		c.627+12697C>T		intron	N/A	ENSP00000506943.1	Q9BX63-1
	BRIP1	ENST00000683039.1		c.627+12697C>T		intron	N/A	ENSP00000508303.1	Q9BX63-1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22947 AN: 151838 Hom.: 2195 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.151 AC: 22964 AN: 151952 Hom.: 2200 Cov.: 31 AF XY: 0.158 AC XY: 11705 AN XY: 74254

African (AFR) AF: 0.107 AC: 4443 AN: 41444

American (AMR) AF: 0.150 AC: 2294 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3462

East Asian (EAS) AF: 0.564 AC: 2908 AN: 5154

South Asian (SAS) AF: 0.159 AC: 766 AN: 4822

European-Finnish (FIN) AF: 0.245 AC: 2573 AN: 10494

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9052 AN: 67988

Other (OTH) AF: 0.157 AC: 331 AN: 2108

Alfa AF: 0.137 Hom.: 973

Bravo AF: 0.147

Asia WGS AF: 0.327 AC: 1134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.55
PhyloP100		-0.034
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: rs2378908; hg19: chr17-59911765;