rs6026577
Positions:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBS1
The NM_016592.5(GNAS):c.*43-9358C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 152,244 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0020 ( 0 hom., cov: 33)
Consequence
GNAS
NM_016592.5 intron
NM_016592.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.198
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 -6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00202 (307/152244) while in subpopulation AFR AF= 0.00686 (285/41522). AF 95% confidence interval is 0.00621. There are 0 homozygotes in gnomad4. There are 141 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNAS | NM_016592.5 | c.*43-9358C>T | intron_variant | ENST00000371075.7 | |||
GNAS | NM_080425.4 | c.2069-9358C>T | intron_variant | ENST00000371100.9 | |||
LOC101927932 | NR_126334.1 | n.37+2520G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAS | ENST00000371075.7 | c.*43-9358C>T | intron_variant | 1 | NM_016592.5 | ||||
GNAS | ENST00000371100.9 | c.2069-9358C>T | intron_variant | 5 | NM_080425.4 | ||||
ENST00000441270.6 | n.19+2520G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00199 AC: 303AN: 152126Hom.: 0 Cov.: 33
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33
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.00202 AC: 307AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.00189 AC XY: 141AN XY: 74446
GnomAD4 genome
?
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33
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141
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74446
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at