4-89827044-T-A

Position:

• chr4-89827044-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000345.4(SNCA):​c.163+1099A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,136 control chromosomes in the GnomAD database, including 27,244 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 0.59 (27244 hom., cov: 33)
• Consequence: SNCA NM_000345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCA	NM_000345.4	c.163+1099A>T		intron_variant		ENST00000394991.8	NP_000336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCA	ENST00000394991.8	c.163+1099A>T		intron_variant		1	NM_000345.4	ENSP00000378442	P1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89592 AN: 152018 Hom.: 27219 Cov.: 33

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.589 AC: 89659 AN: 152136 Hom.: 27244 Cov.: 33 AF XY: 0.589 AC XY: 43830 AN XY: 74368

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.563

Alfa AF: 0.396 Hom.: 998

Bravo AF: 0.597

Asia WGS AF: 0.695 AC: 2409 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.37

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

LitVar

Other links and lift over

dbSNP: rs920624; hg19: chr4-90748195;