Genetic Variant BANK1:p.Cys650Arg (chr4-102043886-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017935.5(BANK1):c.1948T>C(p.Cys650Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.988 in 1,599,810 control chromosomes in the GnomAD database, including 780,967 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.99 ( 74691 hom., cov: 31)

Exomes 𝑓: 0.99 ( 706276 hom. )

Consequence

BANK1
NM_017935.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.633

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.45321E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5 link	c.1948T>C	p.Cys650Arg	missense_variant	Exon 11 of 17	ENST00000322953.9	NP_060405.5	Q8NDB2-1
BANK1	NM_001083907.3 link	c.1858T>C	p.Cys620Arg	missense_variant	Exon 11 of 17		NP_001077376.3	Q8NDB2-3
BANK1	NM_001127507.3 link	c.1549T>C	p.Cys517Arg	missense_variant	Exon 10 of 16		NP_001120979.3	Q8NDB2-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9 link	c.1948T>C	p.Cys650Arg	missense_variant	Exon 11 of 17	1	NM_017935.5	ENSP00000320509.4		Q8NDB2-1

Frequencies

GnomAD3 genomes

AF:

0.991

AC:

150635

AN:

152020

Hom.:

74633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.998

Gnomad AMI

AF:

0.979

Gnomad AMR

AF:

0.995

Gnomad ASJ

AF:

0.990

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.997

Gnomad FIN

AF:

0.981

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.986

Gnomad OTH

AF:

0.994

GnomAD3 exomes

AF:

0.991

AC:

248171

AN:

250434

Hom.:

122968

AF XY:

0.991

AC XY:

134144

AN XY:

135362

show subpopulations

Gnomad AFR exome

AF:

0.998

Gnomad AMR exome

AF:

0.997

Gnomad ASJ exome

AF:

0.990

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.997

Gnomad FIN exome

AF:

0.982

Gnomad NFE exome

AF:

0.987

Gnomad OTH exome

AF:

0.991

GnomAD4 exome

AF:

0.988

AC:

1429974

AN:

1447672

Hom.:

706276

Cov.:

AF XY:

0.988

AC XY:

712535

AN XY:

720992

show subpopulations

Gnomad4 AFR exome

AF:

0.998

Gnomad4 AMR exome

AF:

0.997

Gnomad4 ASJ exome

AF:

0.989

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.997

Gnomad4 FIN exome

AF:

0.983

Gnomad4 NFE exome

AF:

0.986

Gnomad4 OTH exome

AF:

0.989

GnomAD4 genome

AF:

0.991

AC:

150752

AN:

152138

Hom.:

74691

Cov.:

AF XY:

0.991

AC XY:

73682

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.998

Gnomad4 AMR

AF:

0.995

Gnomad4 ASJ

AF:

0.990

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.997

Gnomad4 FIN

AF:

0.981

Gnomad4 NFE

AF:

0.986

Gnomad4 OTH

AF:

0.994

Alfa

AF:

0.988

Hom.:

145969

Bravo

AF:

0.992

TwinsUK

AF:

0.985

AC:

3654

ALSPAC

AF:

0.988

AC:

3808

ESP6500AA

AF:

0.998

AC:

4397

ESP6500EA

AF:

0.987

AC:

8485

ExAC

AF:

0.992

AC:

120361

Asia WGS

AF:

0.999

AC:

3476

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.2

DANN

Benign

0.21

DEOGEN2

Benign

0.054

.;T;.;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.084

T;T;T;.;T

MetaRNN

Benign

9.5e-7

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

.;N;.;.;.

PrimateAI

Benign

0.21

PROVEAN

Benign

1.9

N;N;N;N;N

REVEL

Benign

0.078

Sift

Benign

0.78

T;T;T;T;T

Sift4G

Benign

0.38

T;T;T;T;T

Polyphen

0.0

B;B;B;B;.

Vest4

0.010

MPC

0.027

ClinPred

0.00026

GERP RS

3.6

Varity_R

0.074

gMVP

0.21

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over