rs12498977

Positions:

• chr4-101848520-G-A

Variant summary

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

The NM_017935.5(BANK1):​c.470-6515G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 152,078 control chromosomes in the GnomAD database, including 795 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 0.079 (795 hom., cov: 33)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BANK1	NM_017935.5	c.470-6515G>A		intron_variant		ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.380-6515G>A		intron_variant			NP_001077376.3
BANK1	NM_001127507.3	c.71-6515G>A		intron_variant			NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.470-6515G>A		intron_variant		1	NM_017935.5	ENSP00000320509	P1

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11959 AN: 151960 Hom.: 793 Cov.: 33

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0693

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0788 AC: 11979 AN: 152078 Hom.: 795 Cov.: 33 AF XY: 0.0832 AC XY: 6186 AN XY: 74316

Gnomad4 AFR AF: 0.0288

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.0980

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0539

Gnomad4 NFE AF: 0.0693

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0689 Hom.: 228

Bravo AF: 0.0881

Asia WGS AF: 0.148 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.5
DANN	Benign	0.44

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: rs12498977; hg19: chr4-102769677;