Genetic Variant BANK1:p.Cys650Gly (chr4-102043886-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017935.5(BANK1):c.1948T>G(p.Cys650Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BANK1
NM_017935.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.633

Publications

24 publications found

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 Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

BANK1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05717808).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017935.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BANK1	NM_017935.5	MANE Select	c.1948T>G	p.Cys650Gly	missense	Exon 11 of 17	NP_060405.5
BANK1	NM_001083907.3		c.1858T>G	p.Cys620Gly	missense	Exon 11 of 17	NP_001077376.3	Q8NDB2-3
BANK1	NM_001127507.3		c.1549T>G	p.Cys517Gly	missense	Exon 10 of 16	NP_001120979.3	Q8NDB2-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BANK1	ENST00000322953.9	TSL:1 MANE Select	c.1948T>G	p.Cys650Gly	missense	Exon 11 of 17	ENSP00000320509.4	Q8NDB2-1
BANK1	ENST00000508653.5	TSL:1	c.1549T>G	p.Cys517Gly	missense	Exon 10 of 15	ENSP00000422314.1	Q8NDB2-4
BANK1	ENST00000504592.5	TSL:2	c.1903T>G	p.Cys635Gly	missense	Exon 15 of 21	ENSP00000421443.1	Q8NDB2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1447884

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721078

African (AFR)

AF:

0.00

AC:

AN:

33132

American (AMR)

AF:

0.00

AC:

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25832

East Asian (EAS)

AF:

0.00

AC:

AN:

39530

South Asian (SAS)

AF:

0.00

AC:

AN:

85408

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100714

Other (OTH)

AF:

0.00

AC:

AN:

59838

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.9

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.058

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.26

M_CAP

Benign

0.013

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.63

PrimateAI

Benign

0.21

PROVEAN

Benign

0.19

REVEL

Benign

0.092

Sift

Benign

0.27

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.077

MutPred

0.17

Gain of MoRF binding (P = 0.0876)

MVP

0.40

MPC

0.023

ClinPred

0.097

GERP RS

3.6

Varity_R

0.060

gMVP

0.19

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over