chr4-89706976-A-G

Position:

• chr4-89706976-A-G

Variant summary

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

The ENST00000673902.1(SNCA):​c.391-4592T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,124 control chromosomes in the GnomAD database, including 46,371 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 0.78 (46371 hom., cov: 32)
• Consequence: SNCA ENST00000673902.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124900602	XR_007058466.1	n.9902-12850A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCA	ENST00000673902.1	c.391-4592T>C		intron_variant				ENSP00000501102.1
ENSG00000251095	ENST00000507916.6	n.256-12850A>G		intron_variant		3
ENSG00000251095	ENST00000508021.5	n.447+15571A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117884 AN: 152006 Hom.: 46327 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.754

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

GnomAD4 genome AF: 0.776 AC: 117982 AN: 152124 Hom.: 46371 Cov.: 32 AF XY: 0.779 AC XY: 57913 AN XY: 74370

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.755

Alfa AF: 0.737 Hom.: 6608

Bravo AF: 0.785

Asia WGS AF: 0.921 AC: 3199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs356180; hg19: chr4-90628127;