Genetic Variant GNAS-AS1:n.819+7488G>A (chr20-58834449-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000601795.1(ENSG00000268333):n.513G>A 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 0.417 in 149,144 control chromosomes in the GnomAD database, including 14,230 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 0.42 ( 14207 hom., cov: 31)

Exomes 𝑓: 0.71 ( 23 hom. )

Consequence

ENSG00000268333
ENST00000601795.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

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:

ENSG00000268333 (HGNC:):

ENSG00000268333 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
GNAS-AS1	NR_190185.1 link	n.892G>A	non_coding_transcript_exon_variant	Exon 5 of 5
GNAS-AS1	NR_002785.3 link	n.818+7488G>A	intron_variant	Intron 4 of 4
GNAS-AS1	NR_185847.1 link	n.672+7488G>A	intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
GNAS-AS1	ENST00000424094.6 link	n.819+7488G>A	intron_variant	Intron 4 of 4	1
ENSG00000268333	ENST00000601795.1 link	n.513G>A	non_coding_transcript_exon_variant	Exon 2 of 2	3
GNAS-AS1	ENST00000443966.2 link	n.2120+4276G>A	intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

62086

AN:

148938

Hom.:

14213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.794

Gnomad SAS

AF:

0.494

Gnomad FIN

AF:

0.543

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.412

GnomAD4 exome

AF:

0.714

AC:

AN:

Hom.:

Cov.:

AF XY:

0.697

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 EAS exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.681

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

0.417

AC:

62091

AN:

149060

Hom.:

14207

Cov.:

AF XY:

0.423

AC XY:

30775

AN XY:

72832

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.474

Gnomad4 ASJ

AF:

0.369

Gnomad4 EAS

AF:

0.794

Gnomad4 SAS

AF:

0.492

Gnomad4 FIN

AF:

0.543

Gnomad4 NFE

AF:

0.461

Gnomad4 OTH

AF:

0.407

Alfa

AF:

0.403

Hom.:

1943

Bravo

AF:

0.401

Asia WGS

AF:

0.551

AC:

1914

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.12

DANN

Benign

0.58

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over