chr4-89716450-G-A

Position:

• chr4-89716450-G-A

Variant summary

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

The ENST00000673902.1(SNCA):​c.390+12744C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,896 control chromosomes in the GnomAD database, including 23,595 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 0.54 (23595 hom., cov: 31)
• Consequence: SNCA ENST00000673902.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

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]

ENSG00000251095 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124900602	XR_007058466.1	n.9902-3376G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCA	ENST00000673902.1	c.390+12744C>T		intron_variant				ENSP00000501102.1
ENSG00000251095	ENST00000507916.6	n.256-3376G>A		intron_variant		3
ENSG00000251095	ENST00000508021.5	n.448-9934G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82608 AN: 151778 Hom.: 23588 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.544 AC: 82647 AN: 151896 Hom.: 23595 Cov.: 31 AF XY: 0.545 AC XY: 40439 AN XY: 74262

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.538

Alfa AF: 0.614 Hom.: 10898

Bravo AF: 0.525

Asia WGS AF: 0.495 AC: 1722 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.19

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs356219; hg19: chr4-90637601;