chr4-102053202-C-T

Variant names:

• chr4-102053202-C-T
• rs10516489
• NM_017935.5:c.1970-7009C>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.1970-7009C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,828 control chromosomes in the GnomAD database, including 8,618 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 0.31 (8618 hom., cov: 32)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.421 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.1970-7009C>T		intron	N/A	NP_060405.5
	BANK1	NM_001083907.3		c.1880-7009C>T		intron	N/A	NP_001077376.3
	BANK1	NM_001127507.3		c.1571-7009C>T		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.1970-7009C>T		intron	N/A	ENSP00000320509.4
	BANK1	ENST00000508653.5	TSL:1	c.1571-7009C>T		intron	N/A	ENSP00000422314.1
	BANK1	ENST00000504592.5	TSL:2	c.1925-7009C>T		intron	N/A	ENSP00000421443.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46929 AN: 151710 Hom.: 8621 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.309 AC: 46921 AN: 151828 Hom.: 8618 Cov.: 32 AF XY: 0.307 AC XY: 22783 AN XY: 74194

African (AFR) AF: 0.101 AC: 4181 AN: 41446

American (AMR) AF: 0.334 AC: 5095 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3468

East Asian (EAS) AF: 0.342 AC: 1761 AN: 5148

South Asian (SAS) AF: 0.437 AC: 2101 AN: 4812

European-Finnish (FIN) AF: 0.348 AC: 3654 AN: 10508

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27502 AN: 67874

Other (OTH) AF: 0.349 AC: 735 AN: 2106

Alfa AF: 0.358 Hom.: 1341

Bravo AF: 0.298

Asia WGS AF: 0.373 AC: 1298 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.46
PhyloP100		-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: rs10516489; hg19: chr4-102974359;