rs532475771
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_016592.5(GNAS):c.*42+13801C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000047 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GNAS
NM_016592.5 intron
NM_016592.5 intron
Scores
14
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.56
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.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.09543678).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAS | NM_080425.4 | c.1422C>A | p.Pro474= | synonymous_variant | 1/13 | ENST00000371100.9 | |
GNAS | NM_016592.5 | c.*42+13801C>A | intron_variant | ENST00000371075.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAS | ENST00000371100.9 | c.1422C>A | p.Pro474= | synonymous_variant | 1/13 | 5 | NM_080425.4 | ||
GNAS | ENST00000371075.7 | c.*42+13801C>A | intron_variant | 1 | NM_016592.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 2AN: 151288Hom.: 0 Cov.: 33 FAILED QC
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33
FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000473 AC: 65AN: 1373710Hom.: 0 Cov.: 34 AF XY: 0.0000413 AC XY: 28AN XY: 677630
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0000132 AC: 2AN: 151288Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 73932
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MutPred
Loss of catalytic residue at P411 (P = 0.004);
MVP
ClinPred
T
GERP RS
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at