chr4-101830023-A-G

Variant names:

• chr4-101830023-A-G
• NM_017935.5:c.286A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017935.5(BANK1):​c.286A>G​(p.Lys96Glu) 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. 13/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.88

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]

ACMG classification

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=0.13482022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.286A>G	p.Lys96Glu	missense_variant	Exon 2 of 17	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.196A>G	p.Lys66Glu	missense_variant	Exon 2 of 17		NP_001077376.3
BANK1	NM_001127507.3	c.71-25012A>G		intron_variant	Intron 1 of 15		NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.286A>G	p.Lys96Glu	missense_variant	Exon 2 of 17	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.286A>G (p.K96E) alteration is located in exon 2 (coding exon 2) of the BANK1 gene. This alteration results from a A to G substitution at nucleotide position 286, causing the lysine (K) at amino acid position 96 to be replaced by a glutamic acid (E). 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	0.079
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;T;.
Eigen	Benign	0.096
Eigen_PC	Benign	0.080
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.62	T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.47	T;T;T
Sift4G	Uncertain	0.029	D;D;D
Polyphen		0.97	D;D;.
Vest4		0.13
MutPred		0.33		.;Gain of helix (P = 0.0425);.;
MVP		0.25
MPC		0.031
ClinPred		0.85	D
GERP RS		4.0
Varity_R		0.17
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-102751180;