4-89836694-C-T
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000345.4(SNCA):c.-26+268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,164 control chromosomes in the GnomAD database, including 3,376 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 0.19 ( 3367 hom., cov: 31)
Exomes 𝑓: 0.29 ( 9 hom. )
Consequence
SNCA
NM_000345.4 intron
NM_000345.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.400
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=-0.78).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SNCA | NM_000345.4 | c.-26+268G>A | intron_variant | ENST00000394991.8 | NP_000336.1 | |||
SNCA-AS1 | NR_045481.1 | n.294C>T | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SNCA | ENST00000394991.8 | c.-26+268G>A | intron_variant | 1 | NM_000345.4 | ENSP00000378442 | P1 | |||
SNCA-AS1 | ENST00000513653.1 | n.287C>T | non_coding_transcript_exon_variant | 1/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.188 AC: 28499AN: 151896Hom.: 3366 Cov.: 31
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GnomAD4 exome AF: 0.287 AC: 43AN: 150Hom.: 9 Cov.: 0 AF XY: 0.250 AC XY: 29AN XY: 116
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GnomAD4 genome AF: 0.188 AC: 28509AN: 152014Hom.: 3367 Cov.: 31 AF XY: 0.185 AC XY: 13725AN XY: 74308
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at