rs41442345

Positions:

• chr4-101759756-G-A
• chr4-101759756-G-C

Variant summary

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

The ENST00000504592.5(BANK1):​c.25+38323G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,790 control chromosomes in the GnomAD database, including 4,297 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 0.23 (4297 hom., cov: 31)
• Consequence: BANK1 ENST00000504592.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 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.25+38323G>A		intron_variant		2		ENSP00000421443

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34515 AN: 151672 Hom.: 4286 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.228 AC: 34575 AN: 151790 Hom.: 4297 Cov.: 31 AF XY: 0.232 AC XY: 17190 AN XY: 74196

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.216

Alfa AF: 0.212 Hom.: 591

Bravo AF: 0.228

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41442345; hg19: chr4-102680913;