chr4-102043288-T-C

Variant names:

• chr4-102043288-T-C
• rs2658529
• NM_017935.5:c.1901-551T>C

Variant summary

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

The NM_017935.5(BANK1):​c.1901-551T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,054 control chromosomes in the GnomAD database, including 1,142 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 0.10 (1142 hom., cov: 32)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 3 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=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.1901-551T>C		intron_variant	Intron 10 of 16	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.1811-551T>C		intron_variant	Intron 10 of 16		NP_001077376.3
BANK1	NM_001127507.3	c.1502-551T>C		intron_variant	Intron 9 of 15		NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.1901-551T>C		intron_variant	Intron 10 of 16	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15626 AN: 151936 Hom.: 1141 Cov.: 32

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.103 AC: 15631 AN: 152054 Hom.: 1142 Cov.: 32 AF XY: 0.107 AC XY: 7986 AN XY: 74330

African (AFR) AF: 0.0219 AC: 909 AN: 41524

American (AMR) AF: 0.201 AC: 3061 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 563 AN: 3464

East Asian (EAS) AF: 0.222 AC: 1149 AN: 5166

South Asian (SAS) AF: 0.114 AC: 550 AN: 4824

European-Finnish (FIN) AF: 0.136 AC: 1440 AN: 10600

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7550 AN: 67940

Other (OTH) AF: 0.126 AC: 266 AN: 2108

Alfa AF: 0.0912 Hom.: 102

Bravo AF: 0.105

Asia WGS AF: 0.149 AC: 519 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.72
PhyloP100		1.3
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: rs2658529; hg19: chr4-102964445;