dbSNP rs75650358: GNAS-AS1:n.896C>T (chr20-58819179-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000424094.6(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
ENST00000424094.6 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.463

Variant links:

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]

GNAS-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	Exon rank
GNAS-AS1	NR_002785.3 link	n.895C>T	non_coding_transcript_exon_variant	Exon 5 of 5
GNAS-AS1	NR_185847.1 link	n.749C>T	non_coding_transcript_exon_variant	Exon 5 of 5
GNAS-AS1	NR_185849.1 link	n.710C>T	non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
GNAS-AS1	ENST00000424094.6 link	n.896C>T	non_coding_transcript_exon_variant	Exon 5 of 5	1
GNAS-AS1	ENST00000631314.2 link	n.361C>T	non_coding_transcript_exon_variant	Exon 3 of 3	5
GNAS-AS1	ENST00000685926.2 link	n.723C>T	non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.00956

AC:

1455

AN:

152188

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0122

AC XY:

1519

AN XY:

124804

show subpopulations

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.:

Cov.:

AF XY:

0.00908

AC XY:

676

AN XY:

74472

show subpopulations

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.:

Bravo

AF:

0.0108

Asia WGS

AF:

0.00520

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over