rs17266594

Positions:

• chr4-101829765-T-C

Variant summary

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

The NM_017935.5(BANK1):​c.71-43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,294,384 control chromosomes in the GnomAD database, including 56,046 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 0.27 (5663 hom., cov: 32)
  • Exomes 𝑓: 0.29 (50383 hom.)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BANK1	NM_017935.5	c.71-43T>C		intron_variant		ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.-20-43T>C		intron_variant			NP_001077376.3
BANK1	NM_001127507.3	c.71-25270T>C		intron_variant			NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.71-43T>C		intron_variant		1	NM_017935.5	ENSP00000320509	P1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40836 AN: 151870 Hom.: 5666 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.270

GnomAD3 exomes AF: 0.252 AC: 29225 AN: 116202 Hom.: 3898 AF XY: 0.253 AC XY: 15527 AN XY: 61448

Gnomad AFR exome AF: 0.228

Gnomad AMR exome AF: 0.168

Gnomad ASJ exome AF: 0.315

Gnomad EAS exome AF: 0.153

Gnomad SAS exome AF: 0.170

Gnomad FIN exome AF: 0.317

Gnomad NFE exome AF: 0.291

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.291 AC: 332053 AN: 1142394 Hom.: 50383 Cov.: 15 AF XY: 0.289 AC XY: 163394 AN XY: 565624

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.176

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.269 AC: 40856 AN: 151990 Hom.: 5663 Cov.: 32 AF XY: 0.266 AC XY: 19790 AN XY: 74312

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.270

Alfa AF: 0.293 Hom.: 2201

Bravo AF: 0.258

Asia WGS AF: 0.204 AC: 710 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs17266594; hg19: chr4-102750922;