4-89837794-A-T

Variant names:

• chr4-89837794-A-T
• rs2301134
• NM_001146055.2:c.-26+458T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001146055.2(SNCA):​c.-26+458T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: SNCA NM_001146055.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

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)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCA	NM_001146055.2	c.-26+458T>A		intron_variant	Intron 1 of 5		NP_001139527.1
SNCA	NM_001375285.1	c.-95+458T>A		intron_variant	Intron 1 of 6		NP_001362214.1
SNCA	XM_011532205.3	c.-26+458T>A		intron_variant	Intron 1 of 4		XP_011530507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCA	ENST00000336904.7	c.-26+458T>A		intron_variant	Intron 1 of 5	2		ENSP00000338345.3
SNCA-AS1	ENST00000501215.1	n.312-467A>T		intron_variant	Intron 1 of 1	2
SNCA-AS1	ENST00000513653.1	n.328-467A>T		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2301134; hg19: chr4-90758945;