rs234630
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000516.7(GNAS):c.531-562T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,972 control chromosomes in the GnomAD database, including 4,765 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 0.23 ( 4765 hom., cov: 32)
Consequence
GNAS
NM_000516.7 intron
NM_000516.7 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.28
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAS | NM_000516.7 | c.531-562T>C | intron_variant | ENST00000371085.8 | |||
GNAS | NM_016592.5 | c.*437-562T>C | intron_variant | ENST00000371075.7 | |||
GNAS | NM_080425.4 | c.2460-562T>C | intron_variant | ENST00000371100.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAS | ENST00000371075.7 | c.*437-562T>C | intron_variant | 1 | NM_016592.5 | ||||
GNAS | ENST00000371085.8 | c.531-562T>C | intron_variant | 1 | NM_000516.7 | ||||
GNAS | ENST00000371100.9 | c.2460-562T>C | intron_variant | 5 | NM_080425.4 |
Frequencies
GnomAD3 genomes ? AF: 0.229 AC: 34747AN: 151854Hom.: 4761 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.229 AC: 34744AN: 151972Hom.: 4765 Cov.: 32 AF XY: 0.228 AC XY: 16900AN XY: 74244
GnomAD4 genome
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16900
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74244
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688
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
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