4-89721993-C-T

Variant names:

• chr4-89721993-C-T
• rs168552
• ENST00000673902.1:c.390+7201G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000673902.1(SNCA):​c.390+7201G>A variant causes a intron 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: SNCA ENST00000673902.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant Parkinson disease 4

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Parkinson disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
• autosomal dominant Parkinson disease 1

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• Lewy body dementia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• hereditary late onset Parkinson disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• parkinsonian-pyramidal syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124900602 (HGNC:):

ENSG00000251095 (HGNC:53614):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000673902.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCA	ENST00000673902.1		c.390+7201G>A		intron	N/A	ENSP00000501102.1	A0A669KB41
	ENSG00000251095	ENST00000508021.5	TSL:4	n.448-4391C>T		intron	N/A
	ENSG00000251095	ENST00000621944.1	TSL:5	n.91+1561C>T		intron	N/A

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

African (AFR) AF: 0.949 AC: 39368 AN: 41478

American (AMR) AF: 0.818 AC: 12489 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2580 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5163 AN: 5170

South Asian (SAS) AF: 0.859 AC: 4133 AN: 4814

European-Finnish (FIN) AF: 0.740 AC: 7804 AN: 10546

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48052 AN: 67972

Other (OTH) AF: 0.782 AC: 1653 AN: 2114

Alfa AF: 0.737 Hom.: 19592

Bravo AF: 0.814

Asia WGS AF: 0.932 AC: 3238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.66
PhyloP100		0.072

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs168552;

hg19: chr4-90643144;