Variant chr4-101830194-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017935.5(BANK1):c.457A>G(p.Ile153Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000307 in 1,500,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

BANK1
NM_017935.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0130

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038250387).

BP6

Variant 4-101830194-A-G is Benign according to our data. Variant chr4-101830194-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3260331.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BANK1	NM_017935.5 linkuse as main transcript	c.457A>G	p.Ile153Val	missense_variant	2/17	ENST00000322953.9	NP_060405.5	Q8NDB2-1
BANK1	NM_001083907.3 linkuse as main transcript	c.367A>G	p.Ile123Val	missense_variant	2/17		NP_001077376.3	Q8NDB2-3
BANK1	NM_001127507.3 linkuse as main transcript	c.71-24841A>G		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.457A>G	p.Ile153Val	missense_variant	2/17	1	NM_017935.5	ENSP00000320509.4		Q8NDB2-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000531

AC:

AN:

169570

Hom.:

AF XY:

0.0000744

AC XY:

AN XY:

94120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000628

Gnomad NFE exome

AF:

0.0000920

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000319

AC:

AN:

1347992

Hom.:

Cov.:

AF XY:

0.0000347

AC XY:

AN XY:

662794

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000148

Gnomad4 FIN exome

AF:

0.0000430

Gnomad4 NFE exome

AF:

0.0000368

Gnomad4 OTH exome

AF:

0.0000181

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152008

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000660

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.4

DANN

Benign

0.60

DEOGEN2

Benign

0.087

.;T;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.62

T;T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.038

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.65

.;N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

0.0

N;N;N

REVEL

Benign

0.030

Sift

Benign

0.72

T;T;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.0090

B;B;.

Vest4

0.065

MutPred

0.38

.;Gain of ubiquitination at K156 (P = 0.1278);.;

MVP

0.15

MPC

0.021

ClinPred

0.018

GERP RS

-0.58

Varity_R

0.030

gMVP

0.20

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