rs356164

chr4-89772325-C-G

Variant summary

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

The NM_000345.4(SNCA):c.307-43048G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,148 control chromosomes in the GnomAD database, including 1,187 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 0.11 (1187 hom., cov: 32)
• Consequence: SNCA NM_000345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNCA	NM_000345.4	c.307-43048G>C		intron_variant		ENST00000394991.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNCA	ENST00000394991.8	c.307-43048G>C		intron_variant		1	NM_000345.4	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16767 AN: 152032 Hom.: 1184 Cov.: 32

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.110 AC: 16771 AN: 152148 Hom.: 1187 Cov.: 32 AF XY: 0.112 AC XY: 8342 AN XY: 74360

Gnomad4 AFR AF: 0.0267

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.0882

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.114

Alfa AF: 0.125 Hom.: 198

Bravo AF: 0.108

Asia WGS AF: 0.121 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.19
Dann	Benign	0.52

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: rs356164; hg19: chr4-90693476;