chr4-89836121-G-A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000618500.4(SNCA):c.-26+6C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 243,138 control chromosomes in the GnomAD database, including 40,276 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 0.58 ( 26806 hom., cov: 31)
Exomes 𝑓: 0.53 ( 13470 hom. )
Consequence
SNCA
ENST00000618500.4 splice_donor_region, intron
ENST00000618500.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00004088
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.312
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]
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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 (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SNCA | NM_000345.4 | c.-25-429C>T | intron_variant | ENST00000394991.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SNCA | ENST00000394991.8 | c.-25-429C>T | intron_variant | 1 | NM_000345.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.585 AC: 88711AN: 151688Hom.: 26785 Cov.: 31
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GnomAD4 exome AF: 0.529 AC: 48276AN: 91332Hom.: 13470 Cov.: 0 AF XY: 0.526 AC XY: 25602AN XY: 48632
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GnomAD4 genome ? AF: 0.585 AC: 88773AN: 151806Hom.: 26806 Cov.: 31 AF XY: 0.585 AC XY: 43389AN XY: 74174
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3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 6
Find out detailed SpliceAI scores and Pangolin per-transcript scores at