4-101829919-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017935.5(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. 14/21 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
NM_017935.5 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.566

Publications

171 publications found

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 Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

BANK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017935.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BANK1	NM_017935.5	MANE Select	c.182G>A	p.Arg61His	missense	Exon 2 of 17	NP_060405.5
BANK1	NM_001083907.3		c.92G>A	p.Arg31His	missense	Exon 2 of 17	NP_001077376.3
BANK1	NM_001127507.3		c.71-25116G>A		intron	N/A	NP_001120979.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BANK1	ENST00000322953.9	TSL:1 MANE Select	c.182G>A	p.Arg61His	missense	Exon 2 of 17	ENSP00000320509.4
BANK1	ENST00000508653.5	TSL:1	c.71-25116G>A		intron	N/A	ENSP00000422314.1
BANK1	ENST00000504592.5	TSL:2	c.137G>A	p.Arg46His	missense	Exon 6 of 21	ENSP00000421443.1

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

GnomAD2 exomes

AF:

0.257

AC:

64596

AN:

251048

AF XY:

0.258

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 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

African (AFR)

AF:

0.232

AC:

7752

AN:

33442

American (AMR)

AF:

0.177

AC:

7929

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

9073

AN:

26112

East Asian (EAS)

AF:

0.129

AC:

5096

AN:

39632

South Asian (SAS)

AF:

0.189

AC:

16326

AN:

86192

European-Finnish (FIN)

AF:

0.315

AC:

16796

AN:

53400

Middle Eastern (MID)

AF:

0.227

AC:

1306

AN:

5762

European-Non Finnish (NFE)

AF:

0.309

AC:

343212

AN:

1111180

Other (OTH)

AF:

0.290

AC:

17486

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

15474

30948

46422

61896

77370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11102

22204

33306

44408

55510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.268

AC:

40711

AN:

152032

Hom.:

5617

Cov.:

AF XY:

0.266

AC XY:

19730

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.238

AC:

9864

AN:

41454

American (AMR)

AF:

0.223

AC:

3401

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

1217

AN:

3468

East Asian (EAS)

AF:

0.162

AC:

841

AN:

5182

South Asian (SAS)

AF:

0.189

AC:

909

AN:

4820

European-Finnish (FIN)

AF:

0.323

AC:

3404

AN:

10542

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.298

AC:

20282

AN:

67978

Other (OTH)

AF:

0.268

AC:

564

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1552

3104

4656

6208

7760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.286

Hom.:

24078

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

Sep 15, 2023

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.094

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

PhyloP100

0.57

PrimateAI

Benign

0.17

PROVEAN

Benign

-1.4

REVEL

Benign

0.077

Sift

Benign

0.11

Sift4G

Benign

0.62

Polyphen

0.060

Vest4

0.013

MPC

0.023

ClinPred

0.0074

GERP RS

-1.2

Varity_R

0.042

gMVP

0.15

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over