rs2903269

Positions:

• chr4-101529145-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000504592.5(BANK1):​c.-256+106487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,036 control chromosomes in the GnomAD database, including 7,826 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 0.30 (7826 hom., cov: 32)
• Consequence: BANK1 ENST00000504592.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000504592.5	c.-256+106487C>T		intron_variant		2		ENSP00000421443

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45285 AN: 151920 Hom.: 7804 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.298 AC: 45362 AN: 152036 Hom.: 7826 Cov.: 32 AF XY: 0.299 AC XY: 22255 AN XY: 74326

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.272

Alfa AF: 0.246 Hom.: 3044

Bravo AF: 0.293

Asia WGS AF: 0.278 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.1
DANN	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2903269; hg19: chr4-102450302; COSMIC: COSV73490878;