rs356167

Positions:

• chr4-89752619-A-C
• chr4-89752619-A-G

Variant summary

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

The NM_000345.4(SNCA):​c.307-23342T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,748 control chromosomes in the GnomAD database, including 2,285 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 0.15 (2285 hom., cov: 31)
• Consequence: SNCA NM_000345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.41

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNCA	NM_000345.4	c.307-23342T>G		intron_variant		ENST00000394991.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNCA	ENST00000394991.8	c.307-23342T>G		intron_variant		1	NM_000345.4	P1
	ENST00000615968.1	n.467+706A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23252 AN: 151630 Hom.: 2281 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0923

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.153 AC: 23279 AN: 151748 Hom.: 2285 Cov.: 31 AF XY: 0.158 AC XY: 11699 AN XY: 74136

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0923

Gnomad4 OTH AF: 0.162

Alfa AF: 0.0772 Hom.: 1078

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0040
DANN	Benign	0.45

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: rs356167; hg19: chr4-90673770; COSMIC: COSV61134768; COSMIC: COSV61134768;