4-101829857-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017935.5(BANK1):c.120G>C(p.Trp40Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0167 in 1,596,420 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (17 hom., cov: 32)
  • Exomes 𝑓: 0.017 (259 hom.)
• Consequence: BANK1 NM_017935.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 6.88

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007824212).
• BP6: Variant 4-101829857-G-C is Benign according to our data. Variant chr4-101829857-G-C is described in ClinVar as [Benign]. Clinvar id is 619210.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-101829857-G-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0111 (1695/152230) while in subpopulation NFE AF= 0.0174 (1186/68018). AF 95% confidence interval is 0.0166. There are 17 homozygotes in gnomad4. There are 773 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BANK1	NM_017935.5	c.120G>C	p.Trp40Cys	missense_variant	2/17	ENST00000322953.9
BANK1	NM_001083907.3	c.30G>C	p.Trp10Cys	missense_variant	2/17
BANK1	NM_001127507.3	c.71-25178G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BANK1	ENST00000322953.9	c.120G>C	p.Trp40Cys	missense_variant	2/17	1	NM_017935.5	P1

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1695 AN: 152112 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00799

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0128

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.0117 AC: 2803 AN: 238704 Hom.: 19 AF XY: 0.0115 AC XY: 1484 AN XY: 129166

Gnomad AFR exome AF: 0.00269

Gnomad AMR exome AF: 0.00917

Gnomad ASJ exome AF: 0.0254

Gnomad EAS exome AF: 0.0000565

Gnomad SAS exome AF: 0.00102

Gnomad FIN exome AF: 0.0156

Gnomad NFE exome AF: 0.0162

Gnomad OTH exome AF: 0.0167

GnomAD4 exome AF: 0.0173 AC: 24914 AN: 1444190 Hom.: 259 Cov.: 29 AF XY: 0.0167 AC XY: 12007 AN XY: 718234

Gnomad4 AFR exome AF: 0.00294

Gnomad4 AMR exome AF: 0.00941

Gnomad4 ASJ exome AF: 0.0246

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000940

Gnomad4 FIN exome AF: 0.0146

Gnomad4 NFE exome AF: 0.0197

Gnomad4 OTH exome AF: 0.0182

GnomAD4 genome AF: 0.0111 AC: 1695 AN: 152230 Hom.: 17 Cov.: 32 AF XY: 0.0104 AC XY: 773 AN XY: 74434

Gnomad4 AFR AF: 0.00301

Gnomad4 AMR AF: 0.00798

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0128

Gnomad4 NFE AF: 0.0174

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0168 Hom.: 16

Bravo AF: 0.0112

TwinsUK AF: 0.0208 AC: 77

ALSPAC AF: 0.0215 AC: 83

ESP6500AA AF: 0.00250 AC: 11

ESP6500EA AF: 0.0179 AC: 154

ExAC AF: 0.0101 AC: 1232

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Systemic lupus erythematosus Benign:1

Benign, no assertion criteria provided

research

Carola Vinuesa Lab, John Curtin School of Medical Research

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

BANK1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.31
Cadd	Pathogenic	28
Dann	Uncertain	0.99
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;D
MetaRNN	Benign	0.0078	T;T;T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-9.5	D;D;D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.83
MutPred		0.61		.;Loss of catalytic residue at W40 (P = 7e-04);.;
MPC		0.20
ClinPred		0.060	T
GERP RS		5.2
Varity_R		0.86
gMVP		0.81

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

Other links and lift over

dbSNP: rs35978636; hg19: chr4-102751014; COSMIC: COSV100536015;