rs13129744

Positions:

• chr4-101835574-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017935.5(BANK1):​c.469+5368T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,178 control chromosomes in the GnomAD database, including 4,421 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 0.23 (4421 hom., cov: 33)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BANK1	NM_017935.5	c.469+5368T>C		intron_variant		ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.379+5368T>C		intron_variant			NP_001077376.3
BANK1	NM_001127507.3	c.71-19461T>C		intron_variant			NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.469+5368T>C		intron_variant		1	NM_017935.5	ENSP00000320509	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34891 AN: 152060 Hom.: 4427 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.229 AC: 34888 AN: 152178 Hom.: 4421 Cov.: 33 AF XY: 0.229 AC XY: 17038 AN XY: 74400

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.226

Alfa AF: 0.267 Hom.: 2651

Bravo AF: 0.214

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs13129744; hg19: chr4-102756731;