Genetic Variant GNAS-AS1:n.819+2712C>A (chr20-58839225-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000443966.2(GNAS-AS1):n.1620C>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 0.614 in 398,252 control chromosomes in the GnomAD database, including 76,830 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 0.58 ( 26692 hom., cov: 32)

Exomes 𝑓: 0.63 ( 50138 hom. )

Consequence

GNAS-AS1
ENST00000443966.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.763

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 -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 = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
GNAS-AS1	NR_002785.3 link	n.818+2712C>A	intron_variant	Intron 4 of 4
GNAS-AS1	NR_185847.1 link	n.672+2712C>A	intron_variant	Intron 4 of 4
GNAS-AS1	NR_185848.1 link	n.766+2712C>A	intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
GNAS-AS1	ENST00000424094.6 link	n.819+2712C>A	intron_variant	Intron 4 of 4	1
GNAS-AS1	ENST00000443966.2 link	n.1620C>A	non_coding_transcript_exon_variant	Exon 1 of 2	5
GNAS-AS1	ENST00000598163.1 link	n.388+9654C>A	intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.582

AC:

88356

AN:

151814

Hom.:

26665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.430

Gnomad AMI

AF:

0.724

Gnomad AMR

AF:

0.594

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.802

Gnomad SAS

AF:

0.674

Gnomad FIN

AF:

0.692

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.634

Gnomad OTH

AF:

0.556

GnomAD4 exome

AF:

0.634

AC:

156199

AN:

246320

Hom.:

50138

Cov.:

AF XY:

0.634

AC XY:

79150

AN XY:

124806

show subpopulations

Gnomad4 AFR exome

AF:

0.425

Gnomad4 AMR exome

AF:

0.624

Gnomad4 ASJ exome

AF:

0.507

Gnomad4 EAS exome

AF:

0.755

Gnomad4 SAS exome

AF:

0.662

Gnomad4 FIN exome

AF:

0.693

Gnomad4 NFE exome

AF:

0.629

Gnomad4 OTH exome

AF:

0.609

GnomAD4 genome

AF:

0.582

AC:

88433

AN:

151932

Hom.:

26692

Cov.:

AF XY:

0.587

AC XY:

43581

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.431

Gnomad4 AMR

AF:

0.594

Gnomad4 ASJ

AF:

0.510

Gnomad4 EAS

AF:

0.801

Gnomad4 SAS

AF:

0.675

Gnomad4 FIN

AF:

0.692

Gnomad4 NFE

AF:

0.634

Gnomad4 OTH

AF:

0.561

Alfa

AF:

0.610

Hom.:

8955

Bravo

AF:

0.570

Asia WGS

AF:

0.705

AC:

2449

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

0.72

DANN

Benign

0.74

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