4-102043886-T-C

Variant names:

• chr4-102043886-T-C
• rs3113676
• NM_017935.5:c.1948T>C

Variant summary

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

The NM_017935.5(BANK1):​c.1948T>C​(p.Cys650Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.988 in 1,599,810 control chromosomes in the GnomAD database, including 780,967 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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: 𝑓 0.99 (74691 hom., cov: 31)
  • Exomes 𝑓: 0.99 (706276 hom.)
• Consequence: BANK1 NM_017935.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 24 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=9.45321E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.1948T>C	p.Cys650Arg	missense_variant	Exon 11 of 17	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.1858T>C	p.Cys620Arg	missense_variant	Exon 11 of 17		NP_001077376.3
BANK1	NM_001127507.3	c.1549T>C	p.Cys517Arg	missense_variant	Exon 10 of 16		NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.1948T>C	p.Cys650Arg	missense_variant	Exon 11 of 17	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes AF: 0.991 AC: 150635 AN: 152020 Hom.: 74633 Cov.: 31

Gnomad AFR AF: 0.998

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.995

Gnomad ASJ AF: 0.990

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.997

Gnomad FIN AF: 0.981

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.994

GnomAD2 exomes AF: 0.991 AC: 248171 AN: 250434 AF XY: 0.991

Gnomad AFR exome AF: 0.998

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 0.990

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.982

Gnomad NFE exome AF: 0.987

Gnomad OTH exome AF: 0.991

GnomAD4 exome AF: 0.988 AC: 1429974 AN: 1447672 Hom.: 706276 Cov.: 28 AF XY: 0.988 AC XY: 712535 AN XY: 720992

African (AFR) AF: 0.998 AC: 33067 AN: 33132

American (AMR) AF: 0.997 AC: 44451 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 25541 AN: 25824

East Asian (EAS) AF: 1.00 AC: 39529 AN: 39530

South Asian (SAS) AF: 0.997 AC: 85146 AN: 85402

European-Finnish (FIN) AF: 0.983 AC: 52256 AN: 53140

Middle Eastern (MID) AF: 0.998 AC: 5670 AN: 5684

European-Non Finnish (NFE) AF: 0.986 AC: 1085157 AN: 1100526

Other (OTH) AF: 0.989 AC: 59157 AN: 59834

GnomAD4 genome AF: 0.991 AC: 150752 AN: 152138 Hom.: 74691 Cov.: 31 AF XY: 0.991 AC XY: 73682 AN XY: 74376

African (AFR) AF: 0.998 AC: 41438 AN: 41536

American (AMR) AF: 0.995 AC: 15157 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.990 AC: 3435 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5170 AN: 5170

South Asian (SAS) AF: 0.997 AC: 4808 AN: 4822

European-Finnish (FIN) AF: 0.981 AC: 10414 AN: 10620

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.986 AC: 67048 AN: 67970

Other (OTH) AF: 0.994 AC: 2097 AN: 2110

Alfa AF: 0.988 Hom.: 210258

Bravo AF: 0.992

TwinsUK AF: 0.985 AC: 3654

ALSPAC AF: 0.988 AC: 3808

ESP6500AA AF: 0.998 AC: 4397

ESP6500EA AF: 0.987 AC: 8485

ExAC AF: 0.992 AC: 120361

Asia WGS AF: 0.999 AC: 3476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.2
DANN	Benign	0.21
DEOGEN2	Benign	0.054	.;T;.;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.084	T;T;T;.;T
MetaRNN	Benign	9.5e-7	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	.;N;.;.;.
PhyloP100		0.63
PrimateAI	Benign	0.21	T
PROVEAN	Benign	1.9	N;N;N;N;N
REVEL	Benign	0.078
Sift	Benign	0.78	T;T;T;T;T
Sift4G	Benign	0.38	T;T;T;T;T
Polyphen		0.0	B;B;B;B;.
Vest4		0.010
MPC		0.027
ClinPred		0.00026	T
GERP RS		3.6
Varity_R		0.074
gMVP		0.21
Mutation Taster		=100/0	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: rs3113676; hg19: chr4-102965043; COSMIC: COSV107385507;