4-89715410-G-A

Position:

• chr4-89715410-G-A

Variant summary

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

The ENST00000659878.1(ENSG00000251095):​n.480-10974G>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 0.515 in 151,526 control chromosomes in the GnomAD database, including 21,014 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 0.51 (21014 hom., cov: 30)
• Consequence: ENST00000659878.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124900602	XR_007058466.1	n.9902-4416G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000659878.1	n.480-10974G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78007 AN: 151408 Hom.: 21012 Cov.: 30

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.515 AC: 78031 AN: 151526 Hom.: 21014 Cov.: 30 AF XY: 0.514 AC XY: 38006 AN XY: 73958

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.499

Alfa AF: 0.550 Hom.: 2955

Bravo AF: 0.500

Asia WGS AF: 0.415 AC: 1445 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs356215; hg19: chr4-90636561;