rs3733197

Variant names:

• chr4-101918130-G-A
• rs3733197
• NM_017935.5:c.1147G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-101918130-G-A
• chr4-101918130-G-T

Variant summary

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

The NM_017935.5(BANK1):​c.1147G>A​(p.Ala383Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,604,808 control chromosomes in the GnomAD database, including 95,247 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A383V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.30 (7334 hom., cov: 31)
  • Exomes 𝑓: 0.34 (87913 hom.)
• Consequence: BANK1 NM_017935.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.981
• Publications: 83 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=5.0109625E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017935.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BANK1	NM_017935.5	MANE Select	c.1147G>A	p.Ala383Thr	missense	Exon 7 of 17	NP_060405.5
	BANK1	NM_001083907.3		c.1057G>A	p.Ala353Thr	missense	Exon 7 of 17	NP_001077376.3	Q8NDB2-3
	BANK1	NM_001127507.3		c.748G>A	p.Ala250Thr	missense	Exon 6 of 16	NP_001120979.3	Q8NDB2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BANK1	ENST00000322953.9	TSL:1 MANE Select	c.1147G>A	p.Ala383Thr	missense	Exon 7 of 17	ENSP00000320509.4	Q8NDB2-1
	BANK1	ENST00000508653.5	TSL:1	c.748G>A	p.Ala250Thr	missense	Exon 6 of 15	ENSP00000422314.1	Q8NDB2-4
	BANK1	ENST00000504592.5	TSL:2	c.1102G>A	p.Ala368Thr	missense	Exon 11 of 21	ENSP00000421443.1	Q8NDB2-2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 44890 AN: 151398 Hom.: 7344 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.290

GnomAD2 exomes AF: 0.306 AC: 76388 AN: 249566 AF XY: 0.306

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.216

Gnomad FIN exome AF: 0.436

Gnomad NFE exome AF: 0.364

Gnomad OTH exome AF: 0.323

GnomAD4 exome AF: 0.342 AC: 496390 AN: 1453302 Hom.: 87913 Cov.: 34 AF XY: 0.338 AC XY: 244618 AN XY: 722906

African (AFR) AF: 0.176 AC: 5868 AN: 33280

American (AMR) AF: 0.229 AC: 10187 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 9100 AN: 25836

East Asian (EAS) AF: 0.180 AC: 7135 AN: 39592

South Asian (SAS) AF: 0.192 AC: 16272 AN: 84966

European-Finnish (FIN) AF: 0.431 AC: 22914 AN: 53106

Middle Eastern (MID) AF: 0.259 AC: 1487 AN: 5732

European-Non Finnish (NFE) AF: 0.365 AC: 403932 AN: 1106308

Other (OTH) AF: 0.325 AC: 19495 AN: 59974

GnomAD4 genome AF: 0.296 AC: 44888 AN: 151506 Hom.: 7334 Cov.: 31 AF XY: 0.298 AC XY: 22070 AN XY: 73986

African (AFR) AF: 0.183 AC: 7572 AN: 41390

American (AMR) AF: 0.251 AC: 3813 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1204 AN: 3466

East Asian (EAS) AF: 0.213 AC: 1091 AN: 5120

South Asian (SAS) AF: 0.189 AC: 910 AN: 4804

European-Finnish (FIN) AF: 0.455 AC: 4752 AN: 10452

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.363 AC: 24629 AN: 67776

Other (OTH) AF: 0.288 AC: 607 AN: 2106

Alfa AF: 0.334 Hom.: 25468

Bravo AF: 0.275

TwinsUK AF: 0.374 AC: 1386

ALSPAC AF: 0.366 AC: 1411

ESP6500AA AF: 0.184 AC: 812

ESP6500EA AF: 0.355 AC: 3053

ExAC AF: 0.303 AC: 36740

Asia WGS AF: 0.228 AC: 791 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.00050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.98
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.056
Sift	Benign	0.49	T
Sift4G	Uncertain	0.031	D
Polyphen		0.98	D
Vest4		0.095
MPC		0.025
ClinPred		0.0077	T
GERP RS		1.9
Varity_R		0.028
gMVP		0.32
Mutation Taster		=97/3	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: rs3733197; hg19: chr4-102839287; COSMIC: COSV59840728;