Variant 4-101829820-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017935.5(BANK1):c.83A>T(p.Asp28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000272 in 1,542,590 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

BANK1
NM_017935.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BANK1	NM_017935.5 linkuse as main transcript	c.83A>T	p.Asp28Val	missense_variant	2/17	ENST00000322953.9	NP_060405.5	Q8NDB2-1
BANK1	NM_001083907.3 linkuse as main transcript	c.-8A>T		5_prime_UTR_variant	2/17		NP_001077376.3	Q8NDB2-3
BANK1	NM_001127507.3 linkuse as main transcript	c.71-25215A>T		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.83A>T	p.Asp28Val	missense_variant	2/17	1	NM_017935.5	ENSP00000320509.4		Q8NDB2-1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000289

AC:

AN:

207960

Hom.:

AF XY:

0.00000880

AC XY:

AN XY:

113664

show subpopulations

Gnomad AFR exome

AF:

0.000409

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1390234

Hom.:

Cov.:

AF XY:

0.0000160

AC XY:

AN XY:

689224

show subpopulations

Gnomad4 AFR exome

AF:

0.000629

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000523

GnomAD4 genome

AF:

0.000131

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000457

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:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000196

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2024

The c.83A>T (p.D28V) alteration is located in exon 2 (coding exon 2) of the BANK1 gene. This alteration results from a A to T substitution at nucleotide position 83, causing the aspartic acid (D) at amino acid position 28 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

.;D

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

.;M

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Benign

0.25

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.99

D;D

Vest4

0.71

MVP

0.48

MPC

0.20

ClinPred

0.67

GERP RS

4.0

Varity_R

0.51

gMVP

0.66

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