Variant 4-101918130-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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.

Frequency

Genomes: 𝑓 0.30 ( 7334 hom., cov: 31)

Exomes 𝑓: 0.34 ( 87913 hom. )

Consequence

BANK1
NM_017935.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.981

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
BANK1	NM_017935.5 linkuse as main transcript	c.1147G>A	p.Ala383Thr	missense_variant	7/17	ENST00000322953.9	NP_060405.5	Q8NDB2-1
BANK1	NM_001083907.3 linkuse as main transcript	c.1057G>A	p.Ala353Thr	missense_variant	7/17		NP_001077376.3	Q8NDB2-3
BANK1	NM_001127507.3 linkuse as main transcript	c.748G>A	p.Ala250Thr	missense_variant	6/16		NP_001120979.3	Q8NDB2-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9 linkuse as main transcript	c.1147G>A	p.Ala383Thr	missense_variant	7/17	1	NM_017935.5	ENSP00000320509.4		Q8NDB2-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

44890

AN:

151398

Hom.:

7344

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.338

AC XY:

244618

AN XY:

722906

show subpopulations

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.:

AF XY:

0.298

AC XY:

22070

AN XY:

73986

show subpopulations

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

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.19

.;T;.;.;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.63

T;T;T;.;T

MetaRNN

Benign

0.00050

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;L;.;.;.

PrimateAI

Benign

0.26

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over