4-101528748-A-G

Variant names:

• chr4-101528748-A-G
• rs1426538
• ENST00000504592.5:c.-256+106090A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000504592.5(BANK1):​c.-256+106090A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,806 control chromosomes in the GnomAD database, including 19,989 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 0.50 (19989 hom., cov: 30)
• Consequence: BANK1 ENST00000504592.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000504592.5	c.-256+106090A>G		intron_variant	Intron 2 of 20	2		ENSP00000421443.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75691 AN: 151688 Hom.: 19937 Cov.: 30

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.499 AC: 75809 AN: 151806 Hom.: 19989 Cov.: 30 AF XY: 0.505 AC XY: 37493 AN XY: 74172

African (AFR) AF: 0.663 AC: 27440 AN: 41408

American (AMR) AF: 0.530 AC: 8091 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1258 AN: 3472

East Asian (EAS) AF: 0.537 AC: 2771 AN: 5158

South Asian (SAS) AF: 0.507 AC: 2430 AN: 4794

European-Finnish (FIN) AF: 0.479 AC: 5027 AN: 10502

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27167 AN: 67902

Other (OTH) AF: 0.471 AC: 994 AN: 2112

Alfa AF: 0.425 Hom.: 24219

Bravo AF: 0.513

Asia WGS AF: 0.556 AC: 1935 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	1.5
DANN	Benign	0.64
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1426538; hg19: chr4-102449905;