rs356222

chr4-89721972-C-T

Variant summary

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

The XR_007058466.1(LOC124900602):n.11849C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,066 control chromosomes in the GnomAD database, including 47,075 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 0.78 (47075 hom., cov: 32)
• Consequence: LOC124900602 XR_007058466.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.737

Genes affected

LOC124900602 (HGNC:):

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124900602	XR_007058466.1	n.11849C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000659878.1	n.480-4412C>T		intron_variant, non_coding_transcript_variant
SNCA	ENST00000673902.1	c.390+7222G>A		intron_variant
	ENST00000508021.5	n.448-4412C>T		intron_variant, non_coding_transcript_variant		4
	ENST00000621944.1	n.91+1540C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118869 AN: 151948 Hom.: 47034 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.782 AC: 118964 AN: 152066 Hom.: 47075 Cov.: 32 AF XY: 0.786 AC XY: 58414 AN XY: 74296

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.765

Alfa AF: 0.727 Hom.: 14929

Bravo AF: 0.789

Asia WGS AF: 0.926 AC: 3219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.5
Dann	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs356222; hg19: chr4-90643123;