4-101928062-T-C

Variant names:

• chr4-101928062-T-C
• rs12331595
• NM_017935.5:c.1206+9873T>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.1206+9873T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,484 control chromosomes in the GnomAD database, including 15,095 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (15095 hom., cov: 31)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972
• Publications: 6 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 (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.532 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BANK1	NM_017935.5	MANE Select	c.1206+9873T>C		intron	N/A	NP_060405.5
	BANK1	NM_001083907.3		c.1116+9873T>C		intron	N/A	NP_001077376.3
	BANK1	NM_001127507.3		c.807+9873T>C		intron	N/A	NP_001120979.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BANK1	ENST00000322953.9	TSL:1 MANE Select	c.1206+9873T>C		intron	N/A	ENSP00000320509.4
	BANK1	ENST00000508653.5	TSL:1	c.807+9873T>C		intron	N/A	ENSP00000422314.1
	BANK1	ENST00000504592.5	TSL:2	c.1161+9873T>C		intron	N/A	ENSP00000421443.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64534 AN: 151366 Hom.: 15089 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.450

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.426 AC: 64559 AN: 151484 Hom.: 15095 Cov.: 31 AF XY: 0.424 AC XY: 31384 AN XY: 74000

African (AFR) AF: 0.226 AC: 9356 AN: 41406

American (AMR) AF: 0.456 AC: 6939 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1742 AN: 3460

East Asian (EAS) AF: 0.428 AC: 2179 AN: 5096

South Asian (SAS) AF: 0.550 AC: 2643 AN: 4806

European-Finnish (FIN) AF: 0.470 AC: 4959 AN: 10560

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35047 AN: 67646

Other (OTH) AF: 0.447 AC: 940 AN: 2102

Alfa AF: 0.458 Hom.: 4142

Bravo AF: 0.419

Asia WGS AF: 0.435 AC: 1516 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.49
DANN	Benign	0.92
PhyloP100		-0.97
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: rs12331595; hg19: chr4-102849219;