rs4276281

Variant names:

• chr4-101825623-C-A
• rs4276281
• NM_017935.5:c.71-4185C>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.71-4185C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,764 control chromosomes in the GnomAD database, including 19,377 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 0.48 (19377 hom., cov: 31)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500
• Publications: 10 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.71-4185C>A		intron_variant	Intron 1 of 16	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.-20-4185C>A		intron_variant	Intron 1 of 16		NP_001077376.3
BANK1	NM_001127507.3	c.71-29412C>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.71-4185C>A		intron_variant	Intron 1 of 16	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73397 AN: 151644 Hom.: 19338 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.484 AC: 73490 AN: 151764 Hom.: 19377 Cov.: 31 AF XY: 0.486 AC XY: 36042 AN XY: 74180

African (AFR) AF: 0.701 AC: 29006 AN: 41406

American (AMR) AF: 0.480 AC: 7324 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1628 AN: 3466

East Asian (EAS) AF: 0.473 AC: 2442 AN: 5164

South Asian (SAS) AF: 0.463 AC: 2230 AN: 4818

European-Finnish (FIN) AF: 0.385 AC: 4065 AN: 10546

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25459 AN: 67806

Other (OTH) AF: 0.467 AC: 983 AN: 2106

Alfa AF: 0.409 Hom.: 50398

Bravo AF: 0.496

Asia WGS AF: 0.523 AC: 1817 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0040
DANN	Benign	0.38
PhyloP100		-0.50
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: rs4276281; hg19: chr4-102746780;