chr4-89836947-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000394986.5(SNCA):​c.-230C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 152,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SNCA
ENST00000394986.5 5_prime_UTR

Scores

1
1

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.214
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]
SNCA-AS1 (HGNC:50600): (SNCA antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 4-89836947-G-A is Benign according to our data. Variant chr4-89836947-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 350107.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 37 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SNCANM_000345.4 linkuse as main transcriptc.-26+15C>T intron_variant ENST00000394991.8
SNCA-AS1NR_045481.1 linkuse as main transcriptn.334+213G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SNCAENST00000394991.8 linkuse as main transcriptc.-26+15C>T intron_variant 1 NM_000345.4 P1P37840-1
SNCA-AS1ENST00000513653.1 linkuse as main transcriptn.327+213G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.000223
AC:
34
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000772
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000957
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
240
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
170
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000243
AC:
37
AN:
152314
Hom.:
0
Cov.:
32
AF XY:
0.000228
AC XY:
17
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.000842
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.000242
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Parkinson Disease, Dominant Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
CADD
Benign
17
DANN
Uncertain
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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: rs545809130; hg19: chr4-90758098; API