2-17541387-G-A

Position:

• chr2-17541387-G-A

Variant summary

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

The NM_003385.5(VSNL1):​c.-6+469G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,122 control chromosomes in the GnomAD database, including 8,307 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 0.29 (8307 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: VSNL1 NM_003385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSNL1	NM_003385.5	c.-6+469G>A		intron_variant		ENST00000295156.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSNL1	ENST00000295156.9	c.-6+469G>A		intron_variant		1	NM_003385.5	P1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44399 AN: 152002 Hom.: 8293 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.292 AC: 44437 AN: 152120 Hom.: 8307 Cov.: 32 AF XY: 0.306 AC XY: 22732 AN XY: 74378

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.296

Alfa AF: 0.296 Hom.: 5046

Bravo AF: 0.291

Asia WGS AF: 0.615 AC: 2136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.90

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: rs650275; hg19: chr2-17722654;