rs4640677

Variant names:

• chr4-101736918-G-A
• rs4640677
• ENST00000504592.5:c.25+15485G>A

Variant summary

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

The ENST00000504592.5(BANK1):​c.25+15485G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,862 control chromosomes in the GnomAD database, including 2,693 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 0.18 (2693 hom., cov: 32)
• Consequence: BANK1 ENST00000504592.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760
• Publications: 4 publications found

Genes affected

BANK1 (HGNC:18233): (B cell scaffold protein with ankyrin repeats 1) The protein encoded by this gene is a B-cell-specific scaffold protein that functions in B-cell receptor-induced calcium mobilization from intracellular stores. This protein can also promote Lyn-mediated tyrosine phosphorylation of inositol 1,4,5-trisphosphate receptors. Polymorphisms in this gene are associated with susceptibility to systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

BANK1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

LOC107986297 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107986297	XR_001741778.1	n.194-17115G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000504592.5	c.25+15485G>A		intron_variant	Intron 5 of 20	2		ENSP00000421443.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27698 AN: 151744 Hom.: 2689 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.183 AC: 27736 AN: 151862 Hom.: 2693 Cov.: 32 AF XY: 0.188 AC XY: 13965 AN XY: 74178

African (AFR) AF: 0.167 AC: 6931 AN: 41486

American (AMR) AF: 0.186 AC: 2844 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3462

East Asian (EAS) AF: 0.395 AC: 2030 AN: 5142

South Asian (SAS) AF: 0.190 AC: 915 AN: 4810

European-Finnish (FIN) AF: 0.230 AC: 2418 AN: 10530

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11345 AN: 67854

Other (OTH) AF: 0.179 AC: 378 AN: 2114

Alfa AF: 0.174 Hom.: 1439

Bravo AF: 0.180

Asia WGS AF: 0.277 AC: 964 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.14
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4640677; hg19: chr4-102658075;