2-17587345-G-A

Variant names:

• chr2-17587345-G-A
• rs1033297
• NM_003385.5:c.-5-4725G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VSNL1	NM_003385.5	c.-5-4725G>A		intron_variant	Intron 1 of 3	ENST00000295156.9	NP_003376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSNL1	ENST00000295156.9	c.-5-4725G>A		intron_variant	Intron 1 of 3	1	NM_003385.5	ENSP00000295156.4
VSNL1	ENST00000404666.6	c.-5-4725G>A		intron_variant	Intron 1 of 3	3		ENSP00000384014.1

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

African (AFR) AF: 0.216 AC: 6347 AN: 29428

American (AMR) AF: 0.477 AC: 6572 AN: 13776

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 804 AN: 3224

East Asian (EAS) AF: 0.822 AC: 4139 AN: 5038

South Asian (SAS) AF: 0.434 AC: 1867 AN: 4300

European-Finnish (FIN) AF: 0.429 AC: 3956 AN: 9232

Middle Eastern (MID) AF: 0.133 AC: 32 AN: 240

European-Non Finnish (NFE) AF: 0.282 AC: 17862 AN: 63288

Other (OTH) AF: 0.319 AC: 595 AN: 1864

Alfa AF: 0.273 Hom.: 20349

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
PhyloP100		-0.091
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: rs1033297; hg19: chr2-17768612;