dbSNP rs6064714: GNAS-AS1:n.672+2852T>C (chr20-58839085-A-G) – 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.1760T>C 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 0.127 in 398,438 control chromosomes in the GnomAD database, including 3,533 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 0.13 ( 1291 hom., cov: 31)

Exomes 𝑓: 0.13 ( 2242 hom. )

Consequence

GNAS-AS1
ENST00000443966.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.216

Publications

12 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

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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 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+2852T>C	intron	N/A
GNAS-AS1	NR_002785.3		n.818+2852T>C	intron	N/A
GNAS-AS1	NR_185848.1		n.766+2852T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
GNAS-AS1	ENST00000718285.1	MANE Select	n.672+2852T>C	intron	N/A
GNAS-AS1	ENST00000424094.6	TSL:1	n.819+2852T>C	intron	N/A
GNAS-AS1	ENST00000443966.2	TSL:5	n.1760T>C	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19212

AN:

151992

Hom.:

1291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.0980

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.00213

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.114

GnomAD4 exome

AF:

0.127

AC:

31287

AN:

246328

Hom.:

2242

Cov.:

AF XY:

0.129

AC XY:

16049

AN XY:

124822

show subpopulations

African (AFR)

AF:

0.111

AC:

798

AN:

7180

American (AMR)

AF:

0.0904

AC:

672

AN:

7436

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

1177

AN:

9240

East Asian (EAS)

AF:

0.000262

AC:

AN:

22894

South Asian (SAS)

AF:

0.140

AC:

424

AN:

3030

European-Finnish (FIN)

AF:

0.153

AC:

3193

AN:

20832

Middle Eastern (MID)

AF:

0.111

AC:

144

AN:

1294

European-Non Finnish (NFE)

AF:

0.145

AC:

22859

AN:

158050

Other (OTH)

AF:

0.123

AC:

2014

AN:

16372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1787

3574

5361

7148

8935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

200

300

400

500

<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:

0.126

AC:

19236

AN:

152110

Hom.:

1291

Cov.:

AF XY:

0.128

AC XY:

9536

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.108

AC:

4503

AN:

41510

American (AMR)

AF:

0.0979

AC:

1495

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

467

AN:

3468

East Asian (EAS)

AF:

0.00213

AC:

AN:

5164

South Asian (SAS)

AF:

0.147

AC:

707

AN:

4814

European-Finnish (FIN)

AF:

0.146

AC:

1549

AN:

10586

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.148

AC:

10064

AN:

67976

Other (OTH)

AF:

0.114

AC:

240

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

836

1673

2509

3346

4182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.138

Hom.:

2525

Bravo

AF:

0.120

Asia WGS

AF:

0.0720

AC:

252

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.6

(source)

DANN

Benign

0.77

PhyloP100

-0.22

Mutation Taster

=100/0

polymorphism (auto)

(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