rs3733197

Positions:

• chr4-101918130-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.1147G>A​(p.Ala383Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,604,808 control chromosomes in the GnomAD database, including 95,247 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A383V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.30 (7334 hom., cov: 31)
  • Exomes 𝑓: 0.34 (87913 hom.)
• Consequence: BANK1 NM_017935.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.981

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 (MetaRNN=5.0109625E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BANK1	NM_017935.5	c.1147G>A	p.Ala383Thr	missense_variant	7/17	ENST00000322953.9
BANK1	NM_001083907.3	c.1057G>A	p.Ala353Thr	missense_variant	7/17
BANK1	NM_001127507.3	c.748G>A	p.Ala250Thr	missense_variant	6/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BANK1	ENST00000322953.9	c.1147G>A	p.Ala383Thr	missense_variant	7/17	1	NM_017935.5	P1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 44890 AN: 151398 Hom.: 7344 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.290

GnomAD3 exomes AF: 0.306 AC: 76388 AN: 249566 Hom.: 12695 AF XY: 0.306 AC XY: 41282 AN XY: 134978

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.216

Gnomad SAS exome AF: 0.189

Gnomad FIN exome AF: 0.436

Gnomad NFE exome AF: 0.364

Gnomad OTH exome AF: 0.323

GnomAD4 exome AF: 0.342 AC: 496390 AN: 1453302 Hom.: 87913 Cov.: 34 AF XY: 0.338 AC XY: 244618 AN XY: 722906

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.180

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.431

Gnomad4 NFE exome AF: 0.365

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.296 AC: 44888 AN: 151506 Hom.: 7334 Cov.: 31 AF XY: 0.298 AC XY: 22070 AN XY: 73986

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.288

Alfa AF: 0.343 Hom.: 19099

Bravo AF: 0.275

TwinsUK AF: 0.374 AC: 1386

ALSPAC AF: 0.366 AC: 1411

ESP6500AA AF: 0.184 AC: 812

ESP6500EA AF: 0.355 AC: 3053

ExAC AF: 0.303 AC: 36740

Asia WGS AF: 0.228 AC: 791 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.19	.;T;.;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.63	T;T;T;.;T
MetaRNN	Benign	0.00050	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	.;L;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.056
Sift	Benign	0.49	T;T;T;T;T
Sift4G	Uncertain	0.031	D;D;D;D;D
Polyphen		0.98	D;D;D;D;.
Vest4		0.095
MPC		0.025
ClinPred		0.0077	T
GERP RS		1.9
Varity_R		0.028
gMVP		0.32

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: rs3733197; hg19: chr4-102839287; COSMIC: COSV59840728;