chr3-10292863-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_016362.5(GHRL):c.-787C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,547,364 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
GHRL
NM_016362.5 5_prime_UTR_premature_start_codon_gain
NM_016362.5 5_prime_UTR_premature_start_codon_gain
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.739
Genes affected
GHRL (HGNC:18129): (ghrelin and obestatin prepropeptide) This gene encodes the ghrelin-obestatin preproprotein that is cleaved to yield two peptides, ghrelin and obestatin. Ghrelin is a powerful appetite stimulant and plays an important role in energy homeostasis. Its secretion is initiated when the stomach is empty, whereupon it binds to the growth hormone secretagogue receptor in the hypothalamus which results in the secretion of growth hormone (somatotropin). Ghrelin is thought to regulate multiple activities, including hunger, reward perception via the mesolimbic pathway, gastric acid secretion, gastrointestinal motility, and pancreatic glucose-stimulated insulin secretion. It was initially proposed that obestatin plays an opposing role to ghrelin by promoting satiety and thus decreasing food intake, but this action is still debated. Recent reports suggest multiple metabolic roles for obestatin, including regulating adipocyte function and glucose metabolism. Alternative splicing results in multiple transcript variants. In addition, antisense transcripts for this gene have been identified and may potentially regulate ghrelin-obestatin preproprotein expression. [provided by RefSeq, Nov 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 3-10292863-G-A is Benign according to our data. Variant chr3-10292863-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3257263.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GHRL | NM_016362.5 | c.-787C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/6 | ENST00000335542.13 | NP_057446.1 | ||
GHRL | NM_016362.5 | c.-787C>T | 5_prime_UTR_variant | 1/6 | ENST00000335542.13 | NP_057446.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GHRL | ENST00000335542.13 | c.-787C>T | 5_prime_UTR_premature_start_codon_gain_variant | 1/6 | 1 | NM_016362.5 | ENSP00000335074.8 | |||
GHRL | ENST00000335542.13 | c.-787C>T | 5_prime_UTR_variant | 1/6 | 1 | NM_016362.5 | ENSP00000335074.8 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152090Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000388 AC: 6AN: 154712Hom.: 0 AF XY: 0.0000610 AC XY: 5AN XY: 82010
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GnomAD4 exome AF: 0.000148 AC: 206AN: 1395156Hom.: 0 Cov.: 28 AF XY: 0.000153 AC XY: 105AN XY: 688396
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74422
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | GHRL: BP4, BP7 - |
Computational scores
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Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at