chr4-89718364-G-T

Variant names:

• chr4-89718364-G-T
• rs11931074
• ENST00000673902.1:c.390+10830C>A

Variant summary

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

The ENST00000673902.1(SNCA):​c.390+10830C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,174 control chromosomes in the GnomAD database, including 7,584 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 0.24 (7584 hom., cov: 33)
• Consequence: SNCA ENST00000673902.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124900602	XR_007058466.1	n.9902-1462G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCA	ENST00000673902.1	c.390+10830C>A		intron_variant	Intron 5 of 6			ENSP00000501102.1
ENSG00000251095	ENST00000507916.6	n.256-1462G>T		intron_variant	Intron 2 of 2	3
ENSG00000251095	ENST00000508021.5	n.448-8020G>T		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36572 AN: 152056 Hom.: 7566 Cov.: 33

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.241 AC: 36630 AN: 152174 Hom.: 7584 Cov.: 33 AF XY: 0.244 AC XY: 18127 AN XY: 74410

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0703

Gnomad4 OTH AF: 0.228

Alfa AF: 0.108 Hom.: 2795

Bravo AF: 0.268

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.060
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11931074; hg19: chr4-90639515;