dbSNP rs149847841: BANK1:p.Asp28Ala (chr4-101829820-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017935.5(BANK1):c.83A>C(p.Asp28Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000467 in 1,542,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D28V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

BANK1
NM_017935.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02685675).

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.83A>C	p.Asp28Ala	missense	Exon 2 of 17	NP_060405.5
BANK1	NM_001083907.3		c.-8A>C		5_prime_UTR	Exon 2 of 17	NP_001077376.3	Q8NDB2-3
BANK1	NM_001127507.3		c.71-25215A>C		intron	N/A	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.83A>C	p.Asp28Ala	missense	Exon 2 of 17	ENSP00000320509.4	Q8NDB2-1
BANK1	ENST00000508653.5	TSL:1	c.71-25215A>C		intron	N/A	ENSP00000422314.1	Q8NDB2-4
BANK1	ENST00000504592.5	TSL:2	c.38A>C	p.Asp13Ala	missense	Exon 6 of 21	ENSP00000421443.1	Q8NDB2-2

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000866

AC:

AN:

207960

AF XY:

0.0000704

show subpopulations

Gnomad AFR exome

AF:

0.00123

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000180

AC:

AN:

1390234

Hom.:

Cov.:

AF XY:

0.0000189

AC XY:

AN XY:

689224

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

30214

American (AMR)

AF:

0.00

AC:

AN:

31248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23072

East Asian (EAS)

AF:

0.00

AC:

AN:

38942

South Asian (SAS)

AF:

0.00

AC:

AN:

76702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51642

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5494

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1075598

Other (OTH)

AF:

0.0000174

AC:

AN:

57322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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

AF:

0.000308

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41586

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000376

Hom.:

Bravo

AF:

0.000348

ESP6500AA

AF:

0.000467

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000825

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.037

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.68

M_CAP

Benign

0.012

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

2.2

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.14

Sift

Benign

0.077

Sift4G

Uncertain

0.018

Polyphen

0.21

Vest4

0.30

MVP

0.45

MPC

0.19

ClinPred

0.16

GERP RS

4.0

Varity_R

0.23

gMVP

0.60

Mutation Taster

=76/24

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over