4-101933953-G-C

Variant names:

• chr4-101933953-G-C
• rs13125328
• NM_017935.5:c.1206+15764G>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+15764G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 151,118 control chromosomes in the GnomAD database, including 474 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 0.065 (474 hom., cov: 31)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BANK1	NM_017935.5	c.1206+15764G>C		intron_variant	Intron 7 of 16	ENST00000322953.9	NP_060405.5
BANK1	NM_001083907.3	c.1116+15764G>C		intron_variant	Intron 7 of 16		NP_001077376.3
BANK1	NM_001127507.3	c.807+15764G>C		intron_variant	Intron 6 of 15		NP_001120979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BANK1	ENST00000322953.9	c.1206+15764G>C		intron_variant	Intron 7 of 16	1	NM_017935.5	ENSP00000320509.4

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9810 AN: 151002 Hom.: 475 Cov.: 31

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0813

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.000591

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0483

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.0663

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

GnomAD4 genome AF: 0.0649 AC: 9804 AN: 151118 Hom.: 474 Cov.: 31 AF XY: 0.0624 AC XY: 4607 AN XY: 73806

African (AFR) AF: 0.0168 AC: 693 AN: 41316

American (AMR) AF: 0.0812 AC: 1228 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 522 AN: 3458

East Asian (EAS) AF: 0.000593 AC: 3 AN: 5060

South Asian (SAS) AF: 0.0130 AC: 62 AN: 4756

European-Finnish (FIN) AF: 0.0483 AC: 510 AN: 10566

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0979 AC: 6612 AN: 67540

Other (OTH) AF: 0.0656 AC: 138 AN: 2104

Alfa AF: 0.0127 Hom.: 3

Bravo AF: 0.0680

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.52
DANN	Benign	0.63
PhyloP100		-0.57
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: rs13125328; hg19: chr4-102855110;