4-101829846-G-A

Variant names:

• chr4-101829846-G-A
• NM_017935.5:c.109G>A

Variant summary

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

The NM_017935.5(BANK1):​c.109G>A​(p.Ala37Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 3.81

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.109G>A	p.Ala37Thr	missense_variant	Exon 2 of 17	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.19G>A	p.Ala7Thr	missense_variant	Exon 2 of 17		NP_001077376.3
BANK1	NM_001127507.3	c.71-25189G>A		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.109G>A	p.Ala37Thr	missense_variant	Exon 2 of 17	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.109G>A (p.A37T) alteration is located in exon 2 (coding exon 2) of the BANK1 gene. This alteration results from a G to A substitution at nucleotide position 109, causing the alanine (A) at amino acid position 37 to be replaced by a threonine (T). 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	0.21
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	.;D;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.4	.;M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.72
MutPred		0.42		.;Gain of loop (P = 0.0097);.;
MVP		0.65
MPC		0.18
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.39
gMVP		0.57

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: chr4-102751003;