rs4572885

Positions:

• chr4-101814356-T-A

Variant summary

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

The NM_017935.5(BANK1):​c.71-15452T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,982 control chromosomes in the GnomAD database, including 22,156 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 0.51 (22156 hom., cov: 32)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.583

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BANK1	NM_017935.5	c.71-15452T>A		intron_variant		ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.-21+418T>A		intron_variant			NP_001077376.3
BANK1	NM_001127507.3	c.70+23406T>A		intron_variant			NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.71-15452T>A		intron_variant		1	NM_017935.5	ENSP00000320509	P1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77305 AN: 151864 Hom.: 22101 Cov.: 32

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.509 AC: 77411 AN: 151982 Hom.: 22156 Cov.: 32 AF XY: 0.510 AC XY: 37923 AN XY: 74294

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.473

Alfa AF: 0.447 Hom.: 2081

Bravo AF: 0.520

Asia WGS AF: 0.490 AC: 1704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.094
DANN	Benign	0.52

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: rs4572885; hg19: chr4-102735513; COSMIC: COSV59844407;