chr5-42423817-C-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1
The NM_000163.5(GHR):c.-150C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 164,252 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00019 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00047 ( 0 hom. )
Consequence
GHR
NM_000163.5 5_prime_UTR
NM_000163.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.190
Genes affected
GHR (HGNC:4263): (growth hormone receptor) This gene encodes a member of the type I cytokine receptor family, which is a transmembrane receptor for growth hormone. Binding of growth hormone to the receptor leads to receptor dimerization and the activation of an intra- and intercellular signal transduction pathway leading to growth. Mutations in this gene have been associated with Laron syndrome, also known as the growth hormone insensitivity syndrome (GHIS), a disorder characterized by short stature. In humans and rabbits, but not rodents, growth hormone binding protein (GHBP) is generated by proteolytic cleavage of the extracellular ligand-binding domain from the mature growth hormone receptor protein. Multiple alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 5-42423817-C-A is Benign according to our data. Variant chr5-42423817-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 907634.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000191 (29/151496) while in subpopulation SAS AF= 0.00605 (29/4792). AF 95% confidence interval is 0.00433. There are 1 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GHR | NM_000163.5 | c.-150C>A | 5_prime_UTR_variant | 1/10 | ENST00000230882.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GHR | ENST00000230882.9 | c.-150C>A | 5_prime_UTR_variant | 1/10 | 1 | NM_000163.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000192 AC: 29AN: 151384Hom.: 1 Cov.: 32
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GnomAD4 exome AF: 0.000470 AC: 6AN: 12756Hom.: 0 Cov.: 0 AF XY: 0.000421 AC XY: 4AN XY: 9512
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GnomAD4 genome AF: 0.000191 AC: 29AN: 151496Hom.: 1 Cov.: 32 AF XY: 0.000297 AC XY: 22AN XY: 74012
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Laron-type isolated somatotropin defect Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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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