Genetic Variant BANK1:p.Gly19Ser (chr4-101790935-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017935.5(BANK1):c.55G>A(p.Gly19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000509 in 1,374,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G19C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

BANK1
NM_017935.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.212

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10742429).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BANK1	NM_017935.5	MANE Select	c.55G>A	p.Gly19Ser	missense	Exon 1 of 17	NP_060405.5
	BANK1	NM_001127507.3		c.55G>A	p.Gly19Ser	missense	Exon 1 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.55G>A	p.Gly19Ser	missense	Exon 1 of 17	ENSP00000320509.4	Q8NDB2-1
BANK1	ENST00000508653.5	TSL:1	c.55G>A	p.Gly19Ser	missense	Exon 1 of 15	ENSP00000422314.1	Q8NDB2-4
BANK1	ENST00000428908.5	TSL:5	c.55G>A	p.Gly19Ser	missense	Exon 1 of 16	ENSP00000412748.1	Q8NDB2-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000245

AC:

AN:

122418

AF XY:

0.0000296

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000639

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000509

AC:

AN:

1374600

Hom.:

Cov.:

AF XY:

0.00000590

AC XY:

AN XY:

678028

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30432

American (AMR)

AF:

0.00

AC:

AN:

34138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24124

East Asian (EAS)

AF:

0.00

AC:

AN:

35582

South Asian (SAS)

AF:

0.00

AC:

AN:

77710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35746

Middle Eastern (MID)

AF:

0.000198

AC:

AN:

5060

European-Non Finnish (NFE)

AF:

0.00000558

AC:

AN:

1074594

Other (OTH)

AF:

0.00

AC:

AN:

57214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.062

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.54

M_CAP

Benign

0.072

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

-0.21

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.62

REVEL

Benign

0.076

Sift

Benign

0.12

Sift4G

Benign

0.080

Polyphen

0.95

Vest4

0.14

MutPred

0.20

Gain of glycosylation at G19 (P = 0.0021)

MVP

0.29

MPC

0.17

ClinPred

0.63

GERP RS

0.56

PromoterAI

-0.070

Neutral

(source)

Varity_R

0.050

gMVP

0.31

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over