Variant 4-101870640-G-T 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.899G>T(p.Cys300Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,609,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

BANK1
NM_017935.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.285

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028455943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BANK1	NM_017935.5 linkuse as main transcript	c.899G>T	p.Cys300Phe	missense_variant	5/17	ENST00000322953.9
BANK1	NM_001083907.3 linkuse as main transcript	c.809G>T	p.Cys270Phe	missense_variant	5/17
BANK1	NM_001127507.3 linkuse as main transcript	c.500G>T	p.Cys167Phe	missense_variant	4/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BANK1	ENST00000322953.9 linkuse as main transcript	c.899G>T	p.Cys300Phe	missense_variant	5/17	1	NM_017935.5	P1	Q8NDB2-1

Frequencies

GnomAD3 genomes

AF:

0.000789

AC:

120

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000147

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000158

AC:

AN:

246918

Hom.:

AF XY:

0.0000898

AC XY:

AN XY:

133582

show subpopulations

Gnomad AFR exome

AF:

0.00223

Gnomad AMR exome

AF:

0.0000895

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:

0.0000741

AC:

108

AN:

1457190

Hom.:

Cov.:

AF XY:

0.0000635

AC XY:

AN XY:

724888

show subpopulations

Gnomad4 AFR exome

AF:

0.00262

Gnomad4 AMR exome

AF:

0.000137

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:

0.00000270

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000782

AC:

119

AN:

152120

Hom.:

Cov.:

AF XY:

0.000793

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00272

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.000884

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000198

AC:

Asia WGS

AF:

0.000867

AC:

AN:

3476

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

Mar 14, 2023

The c.899G>T (p.C300F) alteration is located in exon 5 (coding exon 5) of the BANK1 gene. This alteration results from a G to T substitution at nucleotide position 899, causing the cysteine (C) at amino acid position 300 to be replaced by a phenylalanine (F). 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

0.094

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Benign

0.90

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.59

T;T;T;.;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.028

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-8.3

D;D;D;D;D

REVEL

Benign

0.063

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

0.40

B;B;B;B;.

Vest4

0.64

MVP

0.20

MPC

0.029

ClinPred

0.086

GERP RS

-0.035

Varity_R

0.72

gMVP

0.45

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