chr4-101944147-G-A

Variant names:

• chr4-101944147-G-A
• rs13126505
• NM_017935.5:c.1206+25958G>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.1206+25958G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 151,594 control chromosomes in the GnomAD database, including 186 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 0.040 (186 hom., cov: 32)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 47 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.1206+25958G>A		intron_variant	Intron 7 of 16	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.1116+25958G>A		intron_variant	Intron 7 of 16		NP_001077376.3
BANK1	NM_001127507.3	c.807+25958G>A		intron_variant	Intron 6 of 15		NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.1206+25958G>A		intron_variant	Intron 7 of 16	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6112 AN: 151476 Hom.: 186 Cov.: 32

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0500

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.00188

Gnomad FIN AF: 0.00873

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0636

Gnomad OTH AF: 0.0444

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

GnomAD4 genome AF: 0.0403 AC: 6109 AN: 151594 Hom.: 186 Cov.: 32 AF XY: 0.0386 AC XY: 2857 AN XY: 74072

African (AFR) AF: 0.0113 AC: 469 AN: 41418

American (AMR) AF: 0.0500 AC: 758 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3456

East Asian (EAS) AF: 0.000390 AC: 2 AN: 5124

South Asian (SAS) AF: 0.00188 AC: 9 AN: 4794

European-Finnish (FIN) AF: 0.00873 AC: 92 AN: 10536

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0636 AC: 4312 AN: 67792

Other (OTH) AF: 0.0439 AC: 92 AN: 2096

Alfa AF: 0.0552 Hom.: 592

Bravo AF: 0.0443

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.74
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism

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: rs13126505; hg19: chr4-102865304;