20-58833371-C-A

Position:

• chr20-58833371-C-A

Variant summary

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

The NR_002785.2(GNAS-AS1):​n.819+8566G>T 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 0.745 in 152,086 control chromosomes in the GnomAD database, including 42,610 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 0.75 (42610 hom., cov: 31)
• Consequence: GNAS-AS1 NR_002785.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597

Genes affected

GNAS-AS1 (HGNC:24872): (GNAS antisense RNA 1) This gene produces a paternally-imprinted antisense RNA transcript that helps regulate the GNAS complex locus, which encodes the alpha subunit of the stimulatory G protein. Defects in this gene are a cause of pseudohypoparathyroidism type Ib.[provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAS-AS1	NR_002785.2	n.819+8566G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAS-AS1	ENST00000424094.6	n.819+8566G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113261 AN: 151968 Hom.: 42572 Cov.: 31

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.745 AC: 113343 AN: 152086 Hom.: 42610 Cov.: 31 AF XY: 0.746 AC XY: 55458 AN XY: 74334

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.735

Alfa AF: 0.759 Hom.: 54967

Bravo AF: 0.735

Asia WGS AF: 0.757 AC: 2635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.42
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs965808; hg19: chr20-57408426;