4-89838736-A-G

Variant summary

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

The NR_045481.1(SNCA-AS1):n.480+330A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,168 control chromosomes in the GnomAD database, including 3,339 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 (3339 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SNCA-AS1 NR_045481.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325

Genes affected

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNCA-AS1	NR_045481.1	n.480+330A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNCA-AS1	ENST00000513653.1	n.473+330A>G		intron_variant, non_coding_transcript_variant		3
SNCA-AS1	ENST00000501215.1	n.787A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28380 AN: 152050 Hom.: 3337 Cov.: 32

Gnomad AFR AF: 0.0664

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.207

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: 0.187 AC: 28395 AN: 152168 Hom.: 3339 Cov.: 32 AF XY: 0.184 AC XY: 13688 AN XY: 74384

Gnomad4 AFR AF: 0.0663

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.206

Alfa AF: 0.203 Hom.: 1473

Bravo AF: 0.179

Asia WGS AF: 0.0600 AC: 213 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.3
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2619364; hg19: chr4-90759887;