chr4-101829918-C-A

Variant names:

• chr4-101829918-C-A
• NM_017935.5:c.181C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017935.5(BANK1):​c.181C>A​(p.Arg61Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BANK1 NM_017935.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034178138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.181C>A	p.Arg61Ser	missense_variant	Exon 2 of 17	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.91C>A	p.Arg31Ser	missense_variant	Exon 2 of 17		NP_001077376.3
BANK1	NM_001127507.3	c.71-25117C>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.181C>A	p.Arg61Ser	missense_variant	Exon 2 of 17	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.065
DANN	Benign	0.80
DEOGEN2	Benign	0.060	.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.48	T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.034	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.83	.;L;.
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.0080
Sift	Benign	0.43	T;T;T
Sift4G	Benign	0.92	T;T;T
Polyphen		0.034	B;B;.
Vest4		0.088
MutPred		0.41		.;Loss of helix (P = 0.0626);.;
MVP		0.13
MPC		0.023
ClinPred		0.024	T
GERP RS		-2.0
Varity_R		0.11
gMVP		0.19

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: chr4-102751075;