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GeneBe

4-101862610-A-C

Variant summary

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

The NM_017935.5(BANK1):c.709A>C(p.Ile237Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

BANK1
NM_017935.5 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.509
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]

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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=0.14756799).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BANK1NM_017935.5 linkuse as main transcriptc.709A>C p.Ile237Leu missense_variant 4/17 ENST00000322953.9
BANK1NM_001083907.3 linkuse as main transcriptc.619A>C p.Ile207Leu missense_variant 4/17
BANK1NM_001127507.3 linkuse as main transcriptc.310A>C p.Ile104Leu missense_variant 3/16

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BANK1ENST00000322953.9 linkuse as main transcriptc.709A>C p.Ile237Leu missense_variant 4/171 NM_017935.5 P1Q8NDB2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 20, 2023The c.709A>C (p.I237L) alteration is located in exon 4 (coding exon 4) of the BANK1 gene. This alteration results from a A to C substitution at nucleotide position 709, causing the isoleucine (I) at amino acid position 237 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
Cadd
Benign
0.93
Dann
Benign
0.71
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.59
T;T;T;.;T
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.15
T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.85
N;N;N;N;N
REVEL
Benign
0.014
Sift
Benign
0.39
T;T;T;T;T
Sift4G
Benign
0.20
T;T;T;T;T
Polyphen
0.0090
B;B;B;B;.
Vest4
0.15
MutPred
0.25
.;Gain of disorder (P = 0.1036);.;.;.;
MVP
0.29
MPC
0.023
ClinPred
0.068
T
GERP RS
-0.24
Varity_R
0.052
gMVP
0.31

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.

Other links and lift over

dbSNP: rs199571267; hg19: chr4-102783767; COSMIC: COSV59839737; API