2-17544008-A-G

Variant names:

• chr2-17544008-A-G
• rs834504
• NM_003385.5:c.-6+3090A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003385.5(VSNL1):​c.-6+3090A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,962 control chromosomes in the GnomAD database, including 8,310 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 (8310 hom., cov: 32)
• Consequence: VSNL1 NM_003385.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 5 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]

ENSG00000308172 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• 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 rank	MANE	Protein	UniProt
VSNL1	NM_003385.5	c.-6+3090A>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.-6+3090A>G		intron_variant	Intron 1 of 3	1	NM_003385.5	ENSP00000295156.4
VSNL1	ENST00000404666.6	c.-6+4606A>G		intron_variant	Intron 1 of 3	3		ENSP00000384014.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44424 AN: 151844 Hom.: 8296 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.293 AC: 44468 AN: 151962 Hom.: 8310 Cov.: 32 AF XY: 0.306 AC XY: 22734 AN XY: 74252

African (AFR) AF: 0.151 AC: 6252 AN: 41496

American (AMR) AF: 0.445 AC: 6783 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 810 AN: 3470

East Asian (EAS) AF: 0.868 AC: 4469 AN: 5148

South Asian (SAS) AF: 0.416 AC: 2003 AN: 4812

European-Finnish (FIN) AF: 0.410 AC: 4321 AN: 10530

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.280 AC: 19003 AN: 67940

Other (OTH) AF: 0.295 AC: 622 AN: 2110

Alfa AF: 0.288 Hom.: 3518

Bravo AF: 0.292

Asia WGS AF: 0.617 AC: 2145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		0.20
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: rs834504; hg19: chr2-17725275;