dbSNP rs6064714: GNAS-AS1:n.819+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 ENST00000424094.6(GNAS-AS1):n.819+2852T>C variant causes a intron 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
ENST00000424094.6 intron

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
GNAS-AS1	NR_002785.3 link	n.818+2852T>C	intron_variant	Intron 4 of 4
GNAS-AS1	NR_185847.1 link	n.672+2852T>C	intron_variant	Intron 4 of 4
GNAS-AS1	NR_185848.1 link	n.766+2852T>C	intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
GNAS-AS1	ENST00000424094.6 link	n.819+2852T>C	intron_variant	Intron 4 of 4	1
GNAS-AS1	ENST00000443966.2 link	n.1760T>C	non_coding_transcript_exon_variant	Exon 1 of 2	5
GNAS-AS1	ENST00000598163.1 link	n.388+9794T>C	intron_variant	Intron 2 of 3	4

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over