rs356182

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000659878.1(ENSG00000251095):​n.480-21424G>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 0.648 in 151,816 control chromosomes in the GnomAD database, including 32,205 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 0.65 ( 32205 hom., cov: 33)

Consequence


ENST00000659878.1 intron, non_coding_transcript

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.846
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LOC124900602XR_007058466.1 linkuse as main transcriptn.9901+13555G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ENST00000659878.1 linkuse as main transcriptn.480-21424G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.648
AC:
98318
AN:
151698
Hom.:
32183
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.684
Gnomad AMI
AF:
0.659
Gnomad AMR
AF:
0.606
Gnomad ASJ
AF:
0.680
Gnomad EAS
AF:
0.338
Gnomad SAS
AF:
0.640
Gnomad FIN
AF:
0.649
Gnomad MID
AF:
0.742
Gnomad NFE
AF:
0.658
Gnomad OTH
AF:
0.628
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.648
AC:
98392
AN:
151816
Hom.:
32205
Cov.:
33
AF XY:
0.645
AC XY:
47822
AN XY:
74150
show subpopulations
Gnomad4 AFR
AF:
0.684
Gnomad4 AMR
AF:
0.606
Gnomad4 ASJ
AF:
0.680
Gnomad4 EAS
AF:
0.339
Gnomad4 SAS
AF:
0.639
Gnomad4 FIN
AF:
0.649
Gnomad4 NFE
AF:
0.658
Gnomad4 OTH
AF:
0.625
Alfa
AF:
0.640
Hom.:
8653
Bravo
AF:
0.639
Asia WGS
AF:
0.511
AC:
1778
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
6.4
DANN
Benign
0.77

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs356182; hg19: chr4-90626111; API