dbSNP rs778255689: BANK1:p.Cys18Arg (chr4-101790932-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017935.5(BANK1):c.52T>C(p.Cys18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000291 in 1,376,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

BANK1
NM_017935.5 missense

Scores

Clinical Significance

Not reported in ClinVar

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0831005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5 link	c.52T>C	p.Cys18Arg	missense_variant	Exon 1 of 17	ENST00000322953.9	NP_060405.5	Q8NDB2-1
BANK1	NM_001127507.3 link	c.52T>C	p.Cys18Arg	missense_variant	Exon 1 of 16		NP_001120979.3	Q8NDB2-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BANK1	ENST00000322953.9 link	c.52T>C	p.Cys18Arg	missense_variant	Exon 1 of 17	1	NM_017935.5	ENSP00000320509.4	Q8NDB2-1
BANK1	ENST00000508653.5 link	c.52T>C	p.Cys18Arg	missense_variant	Exon 1 of 15	1		ENSP00000422314.1	Q8NDB2-4
BANK1	ENST00000428908.5 link	c.52T>C	p.Cys18Arg	missense_variant	Exon 1 of 16	5		ENSP00000412748.1	Q8NDB2-4
BANK1	ENST00000504592.5 link	c.26-38876T>C		intron_variant	Intron 5 of 20	2		ENSP00000421443.1	Q8NDB2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000291

AC:

AN:

1376650

Hom.:

Cov.:

AF XY:

0.00000589

AC XY:

AN XY:

679138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.0000385

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.3

DANN

Benign

0.85

DEOGEN2

Benign

0.054

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.37

T;T;.

M_CAP

Benign

0.035

MetaRNN

Benign

0.083

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.025

Sift

Benign

0.16

T;D;D

Sift4G

Benign

0.13

T;T;T

Polyphen

0.53

P;P;P

Vest4

0.14

MutPred

0.17

Loss of catalytic residue at P17 (P = 0.0121);Loss of catalytic residue at P17 (P = 0.0121);Loss of catalytic residue at P17 (P = 0.0121);

MVP

0.088

MPC

0.029

ClinPred

0.11

GERP RS

-4.3

Varity_R

0.13

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over