rs10516845

chr4-89763127-A-Gchr4-89763127-A-T

Variant summary

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

The NM_000345.4(SNCA):c.307-33850T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,236 control chromosomes in the GnomAD database, including 1,942 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 0.12 (1942 hom., cov: 32)
• Consequence: SNCA NM_000345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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 (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNCA	NM_000345.4	c.307-33850T>C		intron_variant		ENST00000394991.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNCA	ENST00000394991.8	c.307-33850T>C		intron_variant		1	NM_000345.4	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18649 AN: 152118 Hom.: 1941 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.0897

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0633

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.123 AC: 18661 AN: 152236 Hom.: 1942 Cov.: 32 AF XY: 0.128 AC XY: 9561 AN XY: 74438

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.0897

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0633

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0475 Hom.: 54

Bravo AF: 0.134

Asia WGS AF: 0.398 AC: 1379 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.24
Dann	Benign	0.51

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: rs10516845; hg19: chr4-90684278;