rs2619361

chr4-89836584-C-A

Variant summary

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

The NM_000345.4(SNCA):c.-26+378G>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 152,134 control chromosomes in the GnomAD database, including 3,378 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 (3374 hom., cov: 31)
  • Exomes 𝑓: 0.23 (4 hom.)
• Consequence: SNCA NM_000345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

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]

SNCA-AS1 (HGNC:50600): (SNCA antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNCA	NM_000345.4	c.-26+378G>T		intron_variant		ENST00000394991.8
SNCA-AS1	NR_045481.1	n.184C>A		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNCA	ENST00000394991.8	c.-26+378G>T		intron_variant		1	NM_000345.4	P1
SNCA-AS1	ENST00000513653.1	n.177C>A		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28540 AN: 151886 Hom.: 3373 Cov.: 31

Gnomad AFR AF: 0.0665

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.000970

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.231 AC: 30 AN: 130 Hom.: 4 Cov.: 0 AF XY: 0.207 AC XY: 19 AN XY: 92

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.188 AC: 28550 AN: 152004 Hom.: 3374 Cov.: 31 AF XY: 0.185 AC XY: 13730 AN XY: 74286

Gnomad4 AFR AF: 0.0663

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.000972

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.207

Alfa AF: 0.230 Hom.: 1089

Bravo AF: 0.180

Asia WGS AF: 0.0600 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	7.3
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2619361; hg19: chr4-90757735;