rs6064714

Positions:

• chr20-58839085-A-G

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+2852T>C 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 0.127 in 398,438 control chromosomes in the GnomAD database, including 3,533 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 0.13 (1291 hom., cov: 31)
  • Exomes 𝑓: 0.13 (2242 hom.)
• Consequence: GNAS-AS1 NR_002785.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.216

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNAS-AS1	NR_002785.2	n.819+2852T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNAS-AS1	ENST00000424094.6	n.819+2852T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19212 AN: 151992 Hom.: 1291 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0980

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.127 AC: 31287 AN: 246328 Hom.: 2242 Cov.: 0 AF XY: 0.129 AC XY: 16049 AN XY: 124822

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.0904

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.000262

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.126 AC: 19236 AN: 152110 Hom.: 1291 Cov.: 31 AF XY: 0.128 AC XY: 9536 AN XY: 74354

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0979

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.114

Alfa AF: 0.139 Hom.: 2023

Bravo AF: 0.120

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6064714; hg19: chr20-57414140;