rs12502363

chr4-89791913-G-Achr4-89791913-G-Cchr4-89791913-G-T

Variant summary

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

The NM_000345.4(SNCA):c.306+30333C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,926 control chromosomes in the GnomAD database, including 8,070 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 0.31 (8070 hom., cov: 31)
• Consequence: SNCA NM_000345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

Genes affected

SNCA (HGNC:11138): (synuclein alpha) Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. SNCA may serve to integrate presynaptic signaling and membrane trafficking. Defects in SNCA have been implicated in the pathogenesis of Parkinson disease. SNCA peptides are a major component of amyloid plaques in the brains of patients with Alzheimer's disease. Alternatively spliced transcripts encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNCA	NM_000345.4	c.306+30333C>T		intron_variant		ENST00000394991.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNCA	ENST00000394991.8	c.306+30333C>T		intron_variant		1	NM_000345.4	P1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46611 AN: 151808 Hom.: 8075 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.307 AC: 46603 AN: 151926 Hom.: 8070 Cov.: 31 AF XY: 0.305 AC XY: 22634 AN XY: 74228

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.288

Alfa AF: 0.363 Hom.: 15389

Bravo AF: 0.289

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.26
Dann	Benign	0.39

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: rs12502363; hg19: chr4-90713064;