rs2583987

Positions:

• chr4-89839070-A-C
• chr4-89839070-A-T

Variant summary

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

The ENST00000501215.1(SNCA-AS1):​n.1121A>C 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 0.2 in 140,078 control chromosomes in the GnomAD database, including 3,303 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 0.20 (3303 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: SNCA-AS1 ENST00000501215.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

Genes affected

SNCA-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCA-AS1	NR_045481.1	n.480+664A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCA-AS1	ENST00000501215.1	n.1121A>C		non_coding_transcript_exon_variant	2/2	2
SNCA-AS1	ENST00000513653.1	n.473+664A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 27998 AN: 140000 Hom.: 3303 Cov.: 29

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.00107

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.221

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.200 AC: 28005 AN: 140078 Hom.: 3303 Cov.: 29 AF XY: 0.199 AC XY: 13446 AN XY: 67680

Gnomad4 AFR AF: 0.0744

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.00107

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.220

Alfa AF: 0.186 Hom.: 679

Bravo AF: 0.179

Asia WGS AF: 0.0600 AC: 212 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.3
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2583987; hg19: chr4-90760221;