Genetic Variant ENST00000424094.6:n.819+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 ENST00000424094.6(GNAS-AS1):n.819+7488G>A variant causes a intron 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
ENST00000424094.6 intron

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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
GNAS-AS1	NR_190185.1 link	n.892G>A	non_coding_transcript_exon_variant	Exon 5 of 5
GNAS-AS1	NR_002785.3 link	n.818+7488G>A	intron_variant	Intron 4 of 4
GNAS-AS1	NR_185847.1 link	n.672+7488G>A	intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
GNAS-AS1	ENST00000424094.6 link	n.819+7488G>A	intron_variant	Intron 4 of 4	1
GNAS-AS1	ENST00000601795.1 link	n.513G>A	non_coding_transcript_exon_variant	Exon 2 of 2	3
GNAS-AS1	ENST00000716940.1 link	n.835G>A	non_coding_transcript_exon_variant	Exon 5 of 5

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 v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over