Genetic Variant GNAS-AS1:n.672+7488G>A (chr20-58834449-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000601795.1(GNAS-AS1):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

GNAS-AS1
ENST00000601795.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

pseudohypoparathyroidism type 1B
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

GNAS-AS1 links:

ENSG00000293655 (HGNC:):

ENSG00000293655 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000601795.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000601795.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
GNAS-AS1	NR_185847.1	MANE Select	n.672+7488G>A	intron	N/A
GNAS-AS1	NR_190185.1		n.892G>A	non_coding_transcript_exon	Exon 5 of 5
GNAS-AS1	NR_002785.3		n.818+7488G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
GNAS-AS1	ENST00000718285.1	MANE Select	n.672+7488G>A	intron	N/A
GNAS-AS1	ENST00000424094.6	TSL:1	n.819+7488G>A	intron	N/A
GNAS-AS1	ENST00000601795.1	TSL:3	n.513G>A	non_coding_transcript_exon	Exon 2 of 2

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

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.681

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.417

AC:

62091

AN:

149060

Hom.:

14207

Cov.:

AF XY:

0.423

AC XY:

30775

AN XY:

72832

show subpopulations

African (AFR)

AF:

0.232

AC:

9280

AN:

40012

American (AMR)

AF:

0.474

AC:

7165

AN:

15110

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1261

AN:

3414

East Asian (EAS)

AF:

0.794

AC:

4054

AN:

5108

South Asian (SAS)

AF:

0.492

AC:

2326

AN:

4724

European-Finnish (FIN)

AF:

0.543

AC:

5674

AN:

10448

Middle Eastern (MID)

AF:

0.325

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.461

AC:

30925

AN:

67010

Other (OTH)

AF:

0.407

AC:

835

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1748

3495

5243

6990

8738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.398

Hom.:

1970

Bravo

AF:

0.401

Asia WGS

AF:

0.551

AC:

1914

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.12

(source)

DANN

Benign

0.58

PhyloP100

-1.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over