chr4-101829919-G-A

Variant names:

• chr4-101829919-G-A
• rs10516487
• NM_017935.5:c.182G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017935.5(BANK1):​c.182G>A​(p.Arg61His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,612,802 control chromosomes in the GnomAD database, including 69,684 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R61C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.27 (5617 hom., cov: 32)
  • Exomes 𝑓: 0.29 (64067 hom.)
• Consequence: BANK1 NM_017935.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.566
• Publications: 171 publications found

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]

BANK1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013894141).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.182G>A	p.Arg61His	missense_variant	Exon 2 of 17	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.92G>A	p.Arg31His	missense_variant	Exon 2 of 17		NP_001077376.3
BANK1	NM_001127507.3	c.71-25116G>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.182G>A	p.Arg61His	missense_variant	Exon 2 of 17	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40693 AN: 151914 Hom.: 5621 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.267

GnomAD2 exomes AF: 0.257 AC: 64596 AN: 251048 AF XY: 0.258

Gnomad AFR exome AF: 0.238

Gnomad AMR exome AF: 0.175

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.167

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.297

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.291 AC: 424976 AN: 1460770 Hom.: 64067 Cov.: 35 AF XY: 0.289 AC XY: 209939 AN XY: 726706

African (AFR) AF: 0.232 AC: 7752 AN: 33442

American (AMR) AF: 0.177 AC: 7929 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 9073 AN: 26112

East Asian (EAS) AF: 0.129 AC: 5096 AN: 39632

South Asian (SAS) AF: 0.189 AC: 16326 AN: 86192

European-Finnish (FIN) AF: 0.315 AC: 16796 AN: 53400

Middle Eastern (MID) AF: 0.227 AC: 1306 AN: 5762

European-Non Finnish (NFE) AF: 0.309 AC: 343212 AN: 1111180

Other (OTH) AF: 0.290 AC: 17486 AN: 60358

GnomAD4 genome AF: 0.268 AC: 40711 AN: 152032 Hom.: 5617 Cov.: 32 AF XY: 0.266 AC XY: 19730 AN XY: 74306

African (AFR) AF: 0.238 AC: 9864 AN: 41454

American (AMR) AF: 0.223 AC: 3401 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1217 AN: 3468

East Asian (EAS) AF: 0.162 AC: 841 AN: 5182

South Asian (SAS) AF: 0.189 AC: 909 AN: 4820

European-Finnish (FIN) AF: 0.323 AC: 3404 AN: 10542

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20282 AN: 67978

Other (OTH) AF: 0.268 AC: 564 AN: 2108

Alfa AF: 0.286 Hom.: 24078

Bravo AF: 0.257

TwinsUK AF: 0.317 AC: 1177

ALSPAC AF: 0.312 AC: 1204

ESP6500AA AF: 0.244 AC: 1075

ESP6500EA AF: 0.303 AC: 2610

ExAC AF: 0.255 AC: 30903

Asia WGS AF: 0.205 AC: 715 AN: 3478

EpiCase AF: 0.307

EpiControl AF: 0.303

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Variant of unknown significance Uncertain:1

Sep 15, 2023

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Uncertain	0.98
DEOGEN2	Benign	0.094	.;T;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.54	T;T;T
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	.;N;.
PhyloP100		0.57
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.077
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.62	T;T;T
Polyphen		0.060	B;B;.
Vest4		0.013
MPC		0.023
ClinPred		0.0074	T
GERP RS		-1.2
Varity_R		0.042
gMVP		0.15
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10516487; hg19: chr4-102751076; COSMIC: COSV59840716;