Variant 4-101829919-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 ENST00000322953.9(BANK1):c.182G>A(p.Arg61His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,612,802 control chromosomes in the GnomAD database, including 69,684 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R61C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.27 ( 5617 hom., cov: 32)

Exomes 𝑓: 0.29 ( 64067 hom. )

Consequence

BANK1
ENST00000322953.9 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.566

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=0.0013894141).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
BANK1	NM_017935.5 linkuse as main transcript	c.182G>A	p.Arg61His	missense_variant	2/17	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3 linkuse as main transcript	c.92G>A	p.Arg31His	missense_variant	2/17		NP_001077376.3
BANK1	NM_001127507.3 linkuse as main transcript	c.71-25116G>A		intron_variant			NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9 linkuse as main transcript	c.182G>A	p.Arg61His	missense_variant	2/17	1	NM_017935.5	ENSP00000320509	P1	Q8NDB2-1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40693

AN:

151914

Hom.:

5621

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.267

GnomAD3 exomes

AF:

0.257

AC:

64596

AN:

251048

Hom.:

8904

AF XY:

0.258

AC XY:

34963

AN XY:

135690

show subpopulations

Gnomad AFR exome

AF:

0.238

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.167

Gnomad SAS exome

AF:

0.188

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.297

Gnomad OTH exome

AF:

0.273

GnomAD4 exome

AF:

0.291

AC:

424976

AN:

1460770

Hom.:

64067

Cov.:

AF XY:

0.289

AC XY:

209939

AN XY:

726706

show subpopulations

Gnomad4 AFR exome

AF:

0.232

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.347

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.315

Gnomad4 NFE exome

AF:

0.309

Gnomad4 OTH exome

AF:

0.290

GnomAD4 genome

AF:

0.268

AC:

40711

AN:

152032

Hom.:

5617

Cov.:

AF XY:

0.266

AC XY:

19730

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.238

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.351

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.323

Gnomad4 NFE

AF:

0.298

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.290

Hom.:

12204

Bravo

AF:

0.257

TwinsUK

AF:

0.317

AC:

1177

ALSPAC

AF:

0.312

AC:

1204

ESP6500AA

AF:

0.244

AC:

1075

ESP6500EA

AF:

0.303

AC:

2610

ExAC

AF:

0.255

AC:

30903

Asia WGS

AF:

0.205

AC:

715

AN:

3478

EpiCase

AF:

0.307

EpiControl

AF:

0.303

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Variant of unknown significance

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Sep 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.094

.;T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.54

T;T;T

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

.;N;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.17

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.077

Sift

Benign

0.11

T;T;T

Sift4G

Benign

0.62

T;T;T

Polyphen

0.060

B;B;.

Vest4

0.013

MPC

0.023

ClinPred

0.0074

GERP RS

-1.2

Varity_R

0.042

gMVP

0.15

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over