Variant 4-101790932-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017935.5(BANK1):c.52T>G(p.Cys18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000831 in 1,528,882 control chromosomes in the GnomAD database, including 1 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 (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000081 ( 1 hom. )

Consequence

BANK1
NM_017935.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.45

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028137624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BANK1	NM_017935.5 linkuse as main transcript	c.52T>G	p.Cys18Gly	missense_variant	1/17	ENST00000322953.9	NP_060405.5	Q8NDB2-1
BANK1	NM_001127507.3 linkuse as main transcript	c.52T>G	p.Cys18Gly	missense_variant	1/16		NP_001120979.3	Q8NDB2-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BANK1	ENST00000322953.9 linkuse as main transcript	c.52T>G	p.Cys18Gly	missense_variant	1/17	1	NM_017935.5	ENSP00000320509.4	Q8NDB2-1
BANK1	ENST00000508653.5 linkuse as main transcript	c.52T>G	p.Cys18Gly	missense_variant	1/15	1		ENSP00000422314.1	Q8NDB2-4
BANK1	ENST00000428908.5 linkuse as main transcript	c.52T>G	p.Cys18Gly	missense_variant	1/16	5		ENSP00000412748.1	Q8NDB2-4
BANK1	ENST00000504592.5 linkuse as main transcript	c.26-38876T>G		intron_variant		2		ENSP00000421443.1	Q8NDB2-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000644

AC:

AN:

124216

Hom.:

AF XY:

0.0000437

AC XY:

AN XY:

68716

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:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000806

AC:

111

AN:

1376646

Hom.:

Cov.:

AF XY:

0.0000736

AC XY:

AN XY:

679136

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:

0.00

Gnomad4 FIN exome

AF:

0.0000278

Gnomad4 NFE exome

AF:

0.0000995

Gnomad4 OTH exome

AF:

0.0000524

GnomAD4 genome

AF:

0.000105

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000482

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

Feb 06, 2024

The c.52T>G (p.C18G) alteration is located in exon 1 (coding exon 1) of the BANK1 gene. This alteration results from a T to G substitution at nucleotide position 52, causing the cysteine (C) at amino acid position 18 to be replaced by a glycine (G). 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

Benign

0.049

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.28

DANN

Benign

0.80

DEOGEN2

Benign

0.068

T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.35

T;T;.

M_CAP

Benign

0.022

MetaRNN

Benign

0.028

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.0080

Sift

Benign

0.71

T;D;D

Sift4G

Benign

0.55

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.072

MutPred

0.14

Loss of catalytic residue at P17 (P = 0.0285);Loss of catalytic residue at P17 (P = 0.0285);Loss of catalytic residue at P17 (P = 0.0285);

MVP

0.061

MPC

0.023

ClinPred

0.021

GERP RS

-4.3

Varity_R

0.066

gMVP

0.28

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