chr4-89836694-C-T

Position:

• chr4-89836694-C-T

Variant summary

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

The NM_000345.4(SNCA):​c.-26+268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,164 control chromosomes in the GnomAD database, including 3,376 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 0.19 (3367 hom., cov: 31)
  • Exomes 𝑓: 0.29 (9 hom.)
• Consequence: SNCA NM_000345.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCA	NM_000345.4	c.-26+268G>A		intron_variant		ENST00000394991.8	NP_000336.1
SNCA-AS1	NR_045481.1	n.294C>T		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCA	ENST00000394991.8	c.-26+268G>A		intron_variant		1	NM_000345.4	ENSP00000378442	P1
SNCA-AS1	ENST00000513653.1	n.287C>T		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28499 AN: 151896 Hom.: 3366 Cov.: 31

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.287 AC: 43 AN: 150 Hom.: 9 Cov.: 0 AF XY: 0.250 AC XY: 29 AN XY: 116

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.188 AC: 28509 AN: 152014 Hom.: 3367 Cov.: 31 AF XY: 0.185 AC XY: 13725 AN XY: 74308

Gnomad4 AFR AF: 0.0660

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.205

Alfa AF: 0.193 Hom.: 793

Bravo AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.8
DANN	Benign	0.88

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: rs2619362; hg19: chr4-90757845;