chr2-17578901-A-G

Variant names:

• chr2-17578901-A-G
• rs12470654
• NM_003385.5:c.-5-13169A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BA1

The NM_003385.5(VSNL1):​c.-5-13169A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,108 control chromosomes in the GnomAD database, including 6,591 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 0.28 (6591 hom., cov: 32)
• Consequence: VSNL1 NM_003385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 2 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 -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSNL1	NM_003385.5	c.-5-13169A>G		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.-5-13169A>G		intron_variant	Intron 1 of 3	1	NM_003385.5	ENSP00000295156.4
VSNL1	ENST00000404666.6	c.-5-13169A>G		intron_variant	Intron 1 of 3	3		ENSP00000384014.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42163 AN: 151990 Hom.: 6591 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.277 AC: 42166 AN: 152108 Hom.: 6591 Cov.: 32 AF XY: 0.270 AC XY: 20056 AN XY: 74346

African (AFR) AF: 0.189 AC: 7833 AN: 41516

American (AMR) AF: 0.236 AC: 3602 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1251 AN: 3468

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5174

South Asian (SAS) AF: 0.113 AC: 543 AN: 4820

European-Finnish (FIN) AF: 0.319 AC: 3366 AN: 10566

Middle Eastern (MID) AF: 0.366 AC: 106 AN: 290

European-Non Finnish (NFE) AF: 0.361 AC: 24562 AN: 67966

Other (OTH) AF: 0.290 AC: 613 AN: 2112

Alfa AF: 0.327 Hom.: 6886

Bravo AF: 0.266

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.5
DANN	Benign	0.62
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.54		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.54		Position offset: -5

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

Other links and lift over

dbSNP: rs12470654; hg19: chr2-17760168;