4-101829857-G-C

Position:

chr4-101829857-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017935.5(BANK1):c.120G>C(p.Trp40Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0167 in 1,596,420 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 17 hom., cov: 32)

Exomes 𝑓: 0.017 ( 259 hom. )

Consequence

BANK1
NM_017935.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.88

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007824212).

BP6

Variant 4-101829857-G-C is Benign according to our data. Variant chr4-101829857-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 619210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-101829857-G-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0111 (1695/152230) while in subpopulation NFE AF= 0.0174 (1186/68018). AF 95% confidence interval is 0.0166. There are 17 homozygotes in gnomad4. There are 773 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BANK1	NM_017935.5 linkuse as main transcript	c.120G>C	p.Trp40Cys	missense_variant	2/17	ENST00000322953.9	NP_060405.5	Q8NDB2-1
BANK1	NM_001083907.3 linkuse as main transcript	c.30G>C	p.Trp10Cys	missense_variant	2/17		NP_001077376.3	Q8NDB2-3
BANK1	NM_001127507.3 linkuse as main transcript	c.71-25178G>C		intron_variant			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.120G>C	p.Trp40Cys	missense_variant	2/17	1	NM_017935.5	ENSP00000320509.4		Q8NDB2-1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1695

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00302

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00799

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0128

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0174

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0117

AC:

2803

AN:

238704

Hom.:

AF XY:

0.0115

AC XY:

1484

AN XY:

129166

show subpopulations

Gnomad AFR exome

AF:

0.00269

Gnomad AMR exome

AF:

0.00917

Gnomad ASJ exome

AF:

0.0254

Gnomad EAS exome

AF:

0.0000565

Gnomad SAS exome

AF:

0.00102

Gnomad FIN exome

AF:

0.0156

Gnomad NFE exome

AF:

0.0162

Gnomad OTH exome

AF:

0.0167

GnomAD4 exome

AF:

0.0173

AC:

24914

AN:

1444190

Hom.:

259

Cov.:

AF XY:

0.0167

AC XY:

12007

AN XY:

718234

show subpopulations

Gnomad4 AFR exome

AF:

0.00294

Gnomad4 AMR exome

AF:

0.00941

Gnomad4 ASJ exome

AF:

0.0246

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000940

Gnomad4 FIN exome

AF:

0.0146

Gnomad4 NFE exome

AF:

0.0197

Gnomad4 OTH exome

AF:

0.0182

GnomAD4 genome

AF:

0.0111

AC:

1695

AN:

152230

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

773

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00301

Gnomad4 AMR

AF:

0.00798

Gnomad4 ASJ

AF:

0.0233

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0128

Gnomad4 NFE

AF:

0.0174

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.0168

Hom.:

Bravo

AF:

0.0112

TwinsUK

AF:

0.0208

AC:

ALSPAC

AF:

0.0215

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0179

AC:

154

ExAC

AF:

0.0101

AC:

1232

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	BANK1: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Systemic lupus erythematosus

Benign:1

Benign, no assertion criteria provided

research

Carola Vinuesa Lab, John Curtin School of Medical Research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.72

.;D;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;D;D

MetaRNN

Benign

0.0078

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.4

.;M;.

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-9.5

D;D;D

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.83

MutPred

0.61

.;Loss of catalytic residue at W40 (P = 7e-04);.;

MPC

0.20

ClinPred

0.060

GERP RS

5.2

Varity_R

0.86

gMVP

0.81

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