rs2737033

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000345.4(SNCA):​c.306+35450A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,788 control chromosomes in the GnomAD database, including 3,877 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 0.21 ( 3877 hom., cov: 31)

Consequence

SNCA
NM_000345.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.81

Publications

12 publications found
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 Gene-Disease associations (from GenCC):
  • autosomal dominant Parkinson disease 4
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • Parkinson disease
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
  • autosomal dominant Parkinson disease 1
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • Lewy body dementia
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
  • hereditary late onset Parkinson disease
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • parkinsonian-pyramidal syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNCANM_000345.4 linkc.306+35450A>G intron_variant Intron 4 of 5 ENST00000394991.8 NP_000336.1 P37840-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNCAENST00000394991.8 linkc.306+35450A>G intron_variant Intron 4 of 5 1 NM_000345.4 ENSP00000378442.4 P37840-1

Frequencies

GnomAD3 genomes
AF:
0.214
AC:
32510
AN:
151670
Hom.:
3875
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.143
Gnomad AMI
AF:
0.350
Gnomad AMR
AF:
0.192
Gnomad ASJ
AF:
0.207
Gnomad EAS
AF:
0.000775
Gnomad SAS
AF:
0.121
Gnomad FIN
AF:
0.246
Gnomad MID
AF:
0.152
Gnomad NFE
AF:
0.279
Gnomad OTH
AF:
0.230
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.214
AC:
32534
AN:
151788
Hom.:
3877
Cov.:
31
AF XY:
0.210
AC XY:
15545
AN XY:
74148
show subpopulations
African (AFR)
AF:
0.143
AC:
5941
AN:
41460
American (AMR)
AF:
0.192
AC:
2921
AN:
15212
Ashkenazi Jewish (ASJ)
AF:
0.207
AC:
717
AN:
3468
East Asian (EAS)
AF:
0.000776
AC:
4
AN:
5152
South Asian (SAS)
AF:
0.123
AC:
590
AN:
4798
European-Finnish (FIN)
AF:
0.246
AC:
2578
AN:
10500
Middle Eastern (MID)
AF:
0.156
AC:
46
AN:
294
European-Non Finnish (NFE)
AF:
0.279
AC:
18937
AN:
67886
Other (OTH)
AF:
0.228
AC:
481
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1253
2506
3760
5013
6266
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
332
664
996
1328
1660
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.166
Hom.:
423
Bravo
AF:
0.211
Asia WGS
AF:
0.0670
AC:
235
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.040
DANN
Benign
0.63
PhyloP100
-2.8
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs2737033; hg19: chr4-90707947; API