rs1033297

Positions:

• chr2-17587345-G-A
• chr2-17587345-G-C

Variant summary

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

The NM_003385.5(VSNL1):​c.-5-4725G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 131,162 control chromosomes in the GnomAD database, including 7,634 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 0.32 (7634 hom., cov: 27)
• Consequence: VSNL1 NM_003385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910

Genes affected

VSNL1 (HGNC:12722): (visinin like 1) This gene is a member of the visinin/recoverin subfamily of neuronal calcium sensor proteins. The encoded protein is strongly expressed in granule cells of the cerebellum where it associates with membranes in a calcium-dependent manner and modulates intracellular signaling pathways of the central nervous system by directly or indirectly regulating the activity of adenylyl cyclase. Alternatively spliced transcript variants have been observed, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSNL1	NM_003385.5	c.-5-4725G>A		intron_variant		ENST00000295156.9	NP_003376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSNL1	ENST00000295156.9	c.-5-4725G>A		intron_variant		1	NM_003385.5	ENSP00000295156	P1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 42241 AN: 131078 Hom.: 7618 Cov.: 27

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.322 AC: 42284 AN: 131162 Hom.: 7634 Cov.: 27 AF XY: 0.338 AC XY: 21502 AN XY: 63634

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.319

Alfa AF: 0.275 Hom.: 12892

Bravo AF: 0.284

Asia WGS AF: 0.575 AC: 1964 AN: 3424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.65
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1033297; hg19: chr2-17768612;