rs4572885

Variant names:

• chr4-101814356-T-A
• rs4572885
• NM_017935.5:c.71-15452T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.71-15452T>A		intron_variant	Intron 1 of 16	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.-21+418T>A		intron_variant	Intron 1 of 16		NP_001077376.3
BANK1	NM_001127507.3	c.70+23406T>A		intron_variant	Intron 1 of 15		NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.71-15452T>A		intron_variant	Intron 1 of 16	1	NM_017935.5	ENSP00000320509.4

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

African (AFR) AF: 0.791 AC: 32787 AN: 41456

American (AMR) AF: 0.475 AC: 7259 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1460 AN: 3466

East Asian (EAS) AF: 0.426 AC: 2206 AN: 5174

South Asian (SAS) AF: 0.429 AC: 2066 AN: 4816

European-Finnish (FIN) AF: 0.411 AC: 4342 AN: 10566

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25883 AN: 67908

Other (OTH) AF: 0.473 AC: 997 AN: 2110

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
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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