4-102031709-T-C

Variant names:

• chr4-102031709-T-C
• rs10516491
• NM_017935.5:c.1900+1444T>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.1900+1444T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 152,200 control chromosomes in the GnomAD database, including 717 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 0.061 (717 hom., cov: 32)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374
• Publications: 2 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

ENSG00000251309 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.1900+1444T>C		intron_variant	Intron 10 of 16	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.1810+1444T>C		intron_variant	Intron 10 of 16		NP_001077376.3
BANK1	NM_001127507.3	c.1501+1444T>C		intron_variant	Intron 9 of 15		NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.1900+1444T>C		intron_variant	Intron 10 of 16	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9292 AN: 152082 Hom.: 713 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00953

Gnomad FIN AF: 0.00613

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0439

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

GnomAD4 genome AF: 0.0612 AC: 9308 AN: 152200 Hom.: 717 Cov.: 32 AF XY: 0.0591 AC XY: 4398 AN XY: 74430

African (AFR) AF: 0.176 AC: 7289 AN: 41506

American (AMR) AF: 0.0256 AC: 392 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00954 AC: 46 AN: 4824

European-Finnish (FIN) AF: 0.00613 AC: 65 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0190 AC: 1294 AN: 68004

Other (OTH) AF: 0.0435 AC: 92 AN: 2116

Alfa AF: 0.0433 Hom.: 66

Bravo AF: 0.0671

Asia WGS AF: 0.0130 AC: 48 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.83
PhyloP100		0.37
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: rs10516491; hg19: chr4-102952866;