rs4522865

chr4-101794731-G-Achr4-101794731-G-Cchr4-101794731-G-T

Variant summary

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

The NM_017935.5(BANK1):c.70+3781G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,870 control chromosomes in the GnomAD database, including 29,472 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 0.62 (29472 hom., cov: 32)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BANK1	NM_017935.5	c.70+3781G>A		intron_variant		ENST00000322953.9
BANK1	NM_001127507.3	c.70+3781G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BANK1	ENST00000322953.9	c.70+3781G>A		intron_variant		1	NM_017935.5	P1
BANK1	ENST00000508653.5	c.70+3781G>A		intron_variant		1
BANK1	ENST00000428908.5	c.70+3781G>A		intron_variant		5
BANK1	ENST00000504592.5	c.26-35077G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93444 AN: 151754 Hom.: 29446 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.616 AC: 93520 AN: 151870 Hom.: 29472 Cov.: 32 AF XY: 0.611 AC XY: 45364 AN XY: 74224

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.607

Alfa AF: 0.585 Hom.: 13400

Bravo AF: 0.622

Asia WGS AF: 0.605 AC: 2098 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.0
Dann	Benign	0.70

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: rs4522865; hg19: chr4-102715888;