rs13831
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000516.7(GNAS):c.257+1151A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GNAS
NM_000516.7 intron
NM_000516.7 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.42
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAS | NM_000516.7 | c.257+1151A>C | intron_variant | ENST00000371085.8 | |||
GNAS | NM_016592.5 | c.*160+1151A>C | intron_variant | ENST00000371075.7 | |||
GNAS | NM_080425.4 | c.2186+1151A>C | intron_variant | ENST00000371100.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAS | ENST00000371075.7 | c.*160+1151A>C | intron_variant | 1 | NM_016592.5 | ||||
GNAS | ENST00000371085.8 | c.257+1151A>C | intron_variant | 1 | NM_000516.7 | ||||
GNAS | ENST00000371100.9 | c.2186+1151A>C | intron_variant | 5 | NM_080425.4 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
Cov.:
30
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 419016Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 221588
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
419016
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
221588
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 30
GnomAD4 genome
?
Cov.:
30
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at