4-89721993-C-T

Position:

• chr4-89721993-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.11870C>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 0.803 in 152,030 control chromosomes in the GnomAD database, including 49,971 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 0.80 (49971 hom., cov: 31)
• Consequence: LOC124900602 XR_007058466.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

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.11870C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000659878.1	n.480-4391C>T		intron_variant, non_coding_transcript_variant
SNCA	ENST00000673902.1	c.390+7201G>A		intron_variant
	ENST00000508021.5	n.448-4391C>T		intron_variant, non_coding_transcript_variant		4
	ENST00000621944.1	n.91+1561C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.803 AC: 121994 AN: 151912 Hom.: 49914 Cov.: 31

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.803 AC: 122109 AN: 152030 Hom.: 49971 Cov.: 31 AF XY: 0.806 AC XY: 59887 AN XY: 74292

Gnomad4 AFR AF: 0.949

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.859

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.782

Alfa AF: 0.736 Hom.: 17212

Bravo AF: 0.814

Asia WGS AF: 0.932 AC: 3238 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	2.3
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs168552; hg19: chr4-90643144;