Genetic Variant GNAS-AS1:n.672+2712C>A (chr20-58839225-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

8 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:

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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 = 0.781 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000443966.2. 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+2712C>A	intron	N/A
GNAS-AS1	NR_002785.3		n.818+2712C>A	intron	N/A
GNAS-AS1	NR_185848.1		n.766+2712C>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
GNAS-AS1	ENST00000718285.1	MANE Select	n.672+2712C>A	intron	N/A
GNAS-AS1	ENST00000424094.6	TSL:1	n.819+2712C>A	intron	N/A
GNAS-AS1	ENST00000443966.2	TSL:5	n.1620C>A	non_coding_transcript_exon	Exon 1 of 2

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

African (AFR)

AF:

0.425

AC:

3053

AN:

7180

American (AMR)

AF:

0.624

AC:

4642

AN:

7434

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

4689

AN:

9240

East Asian (EAS)

AF:

0.755

AC:

17296

AN:

22894

South Asian (SAS)

AF:

0.662

AC:

2007

AN:

3032

European-Finnish (FIN)

AF:

0.693

AC:

14437

AN:

20836

Middle Eastern (MID)

AF:

0.529

AC:

684

AN:

1294

European-Non Finnish (NFE)

AF:

0.629

AC:

99425

AN:

158040

Other (OTH)

AF:

0.609

AC:

9966

AN:

16370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

4269

8538

12806

17075

21344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

380

760

1140

1520

1900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.582

AC:

88433

AN:

151932

Hom.:

26692

Cov.:

AF XY:

0.587

AC XY:

43581

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.431

AC:

17836

AN:

41408

American (AMR)

AF:

0.594

AC:

9058

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

1771

AN:

3472

East Asian (EAS)

AF:

0.801

AC:

4132

AN:

5158

South Asian (SAS)

AF:

0.675

AC:

3254

AN:

4820

European-Finnish (FIN)

AF:

0.692

AC:

7310

AN:

10566

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.634

AC:

43099

AN:

67934

Other (OTH)

AF:

0.561

AC:

1187

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1803

3607

5410

7214

9017

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<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:

0.605

Hom.:

11088

Bravo

AF:

0.570

Asia WGS

AF:

0.705

AC:

2449

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

0.72

(source)

DANN

Benign

0.74

PhyloP100

-0.76

PromoterAI

0.0070

Neutral

(source)

Splicing

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over