rs356182

Positions:

• chr4-89704960-G-A
• chr4-89704960-G-C

Variant summary

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

The ENST00000659878.1(ENSG00000251095):​n.480-21424G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,816 control chromosomes in the GnomAD database, including 32,205 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 0.65 (32205 hom., cov: 33)
• Consequence: ENST00000659878.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.846

Genes affected

(HGNC:):

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124900602	XR_007058466.1	n.9901+13555G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000659878.1	n.480-21424G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98318 AN: 151698 Hom.: 32183 Cov.: 33

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.648 AC: 98392 AN: 151816 Hom.: 32205 Cov.: 33 AF XY: 0.645 AC XY: 47822 AN XY: 74150

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.625

Alfa AF: 0.640 Hom.: 8653

Bravo AF: 0.639

Asia WGS AF: 0.511 AC: 1778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.4
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs356182; hg19: chr4-90626111;