rs9998865

Positions:

• chr4-101795989-C-A
• chr4-101795989-C-G
• chr4-101795989-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017935.5(BANK1):​c.70+5039C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,222 control chromosomes in the GnomAD database, including 61,529 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 0.90 (61529 hom., cov: 32)
• Consequence: BANK1 NM_017935.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BANK1	NM_017935.5	c.70+5039C>A		intron_variant		ENST00000322953.9
BANK1	NM_001127507.3	c.70+5039C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BANK1	ENST00000322953.9	c.70+5039C>A		intron_variant		1	NM_017935.5	P1
BANK1	ENST00000508653.5	c.70+5039C>A		intron_variant		1
BANK1	ENST00000428908.5	c.70+5039C>A		intron_variant		5
BANK1	ENST00000504592.5	c.26-33819C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136374 AN: 152104 Hom.: 61483 Cov.: 32

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.894

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.897 AC: 136475 AN: 152222 Hom.: 61529 Cov.: 32 AF XY: 0.890 AC XY: 66233 AN XY: 74404

Gnomad4 AFR AF: 0.977

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.852

Gnomad4 NFE AF: 0.892

Gnomad4 OTH AF: 0.872

Alfa AF: 0.885 Hom.: 20492

Bravo AF: 0.894

Asia WGS AF: 0.831 AC: 2891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.45
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9998865; hg19: chr4-102717146;