rs1372516

Positions:

• chr4-89834579-G-A

Variant summary

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

The NM_000345.4(SNCA):​c.121+968C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,168 control chromosomes in the GnomAD database, including 3,407 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 0.19 (3407 hom., cov: 33)
• Consequence: SNCA NM_000345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCA	NM_000345.4	c.121+968C>T		intron_variant		ENST00000394991.8	NP_000336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCA	ENST00000394991.8	c.121+968C>T		intron_variant		1	NM_000345.4	ENSP00000378442	P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28604 AN: 152050 Hom.: 3405 Cov.: 33

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.188 AC: 28614 AN: 152168 Hom.: 3407 Cov.: 33 AF XY: 0.185 AC XY: 13772 AN XY: 74388

Gnomad4 AFR AF: 0.0652

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.207

Alfa AF: 0.227 Hom.: 545

Bravo AF: 0.180

Asia WGS AF: 0.0610 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.39
DANN	Benign	0.57

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: rs1372516; hg19: chr4-90755730;