NM_017935.5:c.182G>C

Variant names:

• chr4-101829919-G-C
• NM_017935.5:c.182G>C

Variant summary

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

The NM_017935.5(BANK1):​c.182G>C​(p.Arg61Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: BANK1 NM_017935.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566

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=0.053239554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.182G>C	p.Arg61Pro	missense_variant	Exon 2 of 17	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.92G>C	p.Arg31Pro	missense_variant	Exon 2 of 17		NP_001077376.3
BANK1	NM_001127507.3	c.71-25116G>C		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.182G>C	p.Arg61Pro	missense_variant	Exon 2 of 17	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461590 Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3 AN XY: 727102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.2
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.48	T;T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.053	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.49	.;N;.
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.073
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.40	T;T;T
Polyphen		0.0030	B;B;.
Vest4		0.10
MutPred		0.51		.;Loss of helix (P = 0.0123);.;
MVP		0.18
MPC		0.074
ClinPred		0.087	T
GERP RS		-1.2
Varity_R		0.26
gMVP		0.49

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: chr4-102751076;