20-58819179-G-A

Position:

• chr20-58819179-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NR_002785.2(GNAS-AS1):​n.896C>T 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 0.0109 in 398,622 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0095 (13 hom., cov: 32)
  • Exomes 𝑓: 0.012 (34 hom.)
• Consequence: GNAS-AS1 NR_002785.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.463

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 20-58819179-G-A is Benign according to our data. Variant chr20-58819179-G-A is described in ClinVar as [Benign]. Clinvar id is 3341918.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0117 (2885/246316) while in subpopulation MID AF= 0.0595 (77/1294). AF 95% confidence interval is 0.0488. There are 34 homozygotes in gnomad4_exome. There are 1519 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAS-AS1	NR_002785.2	n.896C>T		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAS-AS1	ENST00000424094.6	n.896C>T		non_coding_transcript_exon_variant	5/5	1

Frequencies

GnomAD3 genomes AF: 0.00956 AC: 1455 AN: 152188 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00548

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0380

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0191

GnomAD4 exome AF: 0.0117 AC: 2885 AN: 246316 Hom.: 34 Cov.: 0 AF XY: 0.0122 AC XY: 1519 AN XY: 124804

Gnomad4 AFR exome AF: 0.00710

Gnomad4 AMR exome AF: 0.0136

Gnomad4 ASJ exome AF: 0.0400

Gnomad4 EAS exome AF: 0.0000437

Gnomad4 SAS exome AF: 0.00363

Gnomad4 FIN exome AF: 0.00192

Gnomad4 NFE exome AF: 0.0128

Gnomad4 OTH exome AF: 0.0128

GnomAD4 genome AF: 0.00955 AC: 1454 AN: 152306 Hom.: 13 Cov.: 32 AF XY: 0.00908 AC XY: 676 AN XY: 74472

Gnomad4 AFR AF: 0.00546

Gnomad4 AMR AF: 0.0130

Gnomad4 ASJ AF: 0.0380

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00207 Hom.: 1

Bravo AF: 0.0108

Asia WGS AF: 0.00520 AC: 18 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

GNAS-AS1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs75650358; hg19: chr20-57394234;