4-89713401-A-G

Variant summary

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

The ENST00000659878.1(ENSG00000251095):n.480-12983A>G 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 0.749 in 151,564 control chromosomes in the GnomAD database, including 42,785 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 0.75 (42785 hom., cov: 32)
• Consequence: ENST00000659878.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642

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=-0.91).
• 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	UniProt
LOC124900602	XR_007058466.1	n.9902-6425A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000659878.1	n.480-12983A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113372 AN: 151444 Hom.: 42752 Cov.: 32

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.749 AC: 113463 AN: 151564 Hom.: 42785 Cov.: 32 AF XY: 0.753 AC XY: 55782 AN XY: 74042

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.848

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.730

Alfa AF: 0.713 Hom.: 4848

Bravo AF: 0.753

Asia WGS AF: 0.911 AC: 3164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.56
Dann	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2572323; hg19: chr4-90634552;