rs12648641

Variant names:

• chr4-101738593-C-A
• rs12648641
• ENST00000504592.5:c.25+17160C>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+17160C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,100 control chromosomes in the GnomAD database, including 1,288 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 0.12 (1288 hom., cov: 33)
• Consequence: BANK1 ENST00000504592.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107986297	XR_001741778.1	n.194-15440C>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+17160C>A		intron_variant	Intron 5 of 20	2		ENSP00000421443.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18542 AN: 151982 Hom.: 1286 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0993

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.122 AC: 18576 AN: 152100 Hom.: 1288 Cov.: 33 AF XY: 0.127 AC XY: 9443 AN XY: 74362

African (AFR) AF: 0.135 AC: 5601 AN: 41506

American (AMR) AF: 0.127 AC: 1945 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3472

East Asian (EAS) AF: 0.272 AC: 1406 AN: 5178

South Asian (SAS) AF: 0.152 AC: 735 AN: 4822

European-Finnish (FIN) AF: 0.138 AC: 1456 AN: 10576

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0993 AC: 6751 AN: 67960

Other (OTH) AF: 0.123 AC: 259 AN: 2108

Alfa AF: 0.109 Hom.: 286

Bravo AF: 0.121

Asia WGS AF: 0.221 AC: 765 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.50
DANN	Benign	0.21
PhyloP100		-0.51
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: rs12648641; hg19: chr4-102659750;