rs117849691
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_000516.7(GNAS):c.306G>A(p.Ala102Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000258 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
GNAS
NM_000516.7 synonymous
NM_000516.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.179
Genes affected
GNAS (HGNC:4392): (GNAS complex locus) This locus has a highly complex imprinted expression pattern. It gives rise to maternally, paternally, and biallelically expressed transcripts that are derived from four alternative promoters and 5' exons. Some transcripts contain a differentially methylated region (DMR) at their 5' exons, and this DMR is commonly found in imprinted genes and correlates with transcript expression. An antisense transcript is produced from an overlapping locus on the opposite strand. One of the transcripts produced from this locus, and the antisense transcript, are paternally expressed noncoding RNAs, and may regulate imprinting in this region. In addition, one of the transcripts contains a second overlapping ORF, which encodes a structurally unrelated protein - Alex. Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit, a key element of the classical signal transduction pathway linking receptor-ligand interactions with the activation of adenylyl cyclase and a variety of cellular reponses. Multiple transcript variants encoding different isoforms have been found for this gene. Mutations in this gene result in pseudohypoparathyroidism type 1a, pseudohypoparathyroidism type 1b, Albright hereditary osteodystrophy, pseudopseudohypoparathyroidism, McCune-Albright syndrome, progressive osseus heteroplasia, polyostotic fibrous dysplasia of bone, and some pituitary tumors. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 20-58903579-G-A is Benign according to our data. Variant chr20-58903579-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-58903579-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.179 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0012 (183/152298) while in subpopulation AFR AF= 0.00399 (166/41556). AF 95% confidence interval is 0.0035. There are 0 homozygotes in gnomad4. There are 88 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| GNAS | ENST00000371085.8 | c.306G>A | p.Ala102Ala | synonymous_variant | Exon 4 of 13 | 1 | NM_000516.7 | ENSP00000360126.3 | ||
| GNAS | ENST00000676826.2 | c.2238G>A | p.Ala746Ala | synonymous_variant | Exon 4 of 13 | ENSP00000504675.2 | ||||
| GNAS | ENST00000371102.8 | c.2193G>A | p.Ala731Ala | synonymous_variant | Exon 3 of 12 | 5 | ENSP00000360143.4 | |||
| GNAS | ENST00000354359.12 | c.309G>A | p.Ala103Ala | synonymous_variant | Exon 4 of 13 | 1 | ENSP00000346328.7 | |||
| GNAS | ENST00000371095.7 | c.264G>A | p.Ala88Ala | synonymous_variant | Exon 3 of 12 | 1 | ENSP00000360136.3 | |||
| GNAS | ENST00000470512.6 | c.132G>A | p.Ala44Ala | synonymous_variant | Exon 4 of 13 | 5 | ENSP00000499552.2 | |||
| GNAS | ENST00000480232.6 | c.132G>A | p.Ala44Ala | synonymous_variant | Exon 5 of 14 | 5 | ENSP00000499545.2 | |||
| GNAS | ENST00000663479.2 | c.132G>A | p.Ala44Ala | synonymous_variant | Exon 4 of 13 | ENSP00000499353.2 | ||||
| GNAS | ENST00000462499.6 | c.87G>A | p.Ala29Ala | synonymous_variant | Exon 3 of 12 | 2 | ENSP00000499758.2 | |||
| GNAS | ENST00000467227.6 | c.87G>A | p.Ala29Ala | synonymous_variant | Exon 4 of 13 | 3 | ENSP00000499681.2 | |||
| GNAS | ENST00000478585.6 | c.87G>A | p.Ala29Ala | synonymous_variant | Exon 3 of 12 | 2 | ENSP00000499762.2 | |||
| GNAS | ENST00000481039.6 | c.87G>A | p.Ala29Ala | synonymous_variant | Exon 3 of 12 | 5 | ENSP00000499767.2 | |||
| GNAS | ENST00000485673.6 | c.87G>A | p.Ala29Ala | synonymous_variant | Exon 3 of 12 | 5 | ENSP00000499334.2 | |||
| GNAS | ENST00000488546.6 | c.87G>A | p.Ala29Ala | synonymous_variant | Exon 3 of 12 | 5 | ENSP00000499332.2 | |||
| GNAS | ENST00000492907.6 | c.87G>A | p.Ala29Ala | synonymous_variant | Exon 3 of 12 | 3 | ENSP00000499443.2 | |||
| GNAS | ENST00000371075 | c.*212G>A | 3_prime_UTR_variant | Exon 4 of 12 | 1 | NM_016592.5 | ENSP00000360115.3 | |||
| GNAS | ENST00000461152.6 | c.*176G>A | 3_prime_UTR_variant | Exon 3 of 3 | 5 | ENSP00000499274.1 | ||||
| GNAS | ENST00000453292 | c.*167G>A | 3_prime_UTR_variant | Exon 3 of 11 | 5 | ENSP00000392000.2 |
Frequencies
GnomAD3 genomes 0.00120 AC: 182AN: 152180Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000302 AC: 76AN: 251484Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135916
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GnomAD4 exome AF: 0.000160 AC: 234AN: 1461818Hom.: 0 Cov.: 32 AF XY: 0.000142 AC XY: 103AN XY: 727214
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GnomAD4 genome 0.00120 AC: 183AN: 152298Hom.: 0 Cov.: 31 AF XY: 0.00118 AC XY: 88AN XY: 74472
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Sep 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
GNAS: BP4, BP7 -
Jan 23, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not specified Benign:1
Jun 05, 2017
Genetic Services Laboratory, University of Chicago
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Name
Calibrated prediction
Score
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at