rs34190075
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000163.5(GHR):c.785-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,178,276 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 41 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 17 hom. )
Consequence
GHR
NM_000163.5 splice_polypyrimidine_tract, intron
NM_000163.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0001877
2
Clinical Significance
Conservation
PhyloP100: -0.0490
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 5-42713420-G-A is Benign according to our data. Variant chr5-42713420-G-A is described in ClinVar as [Benign]. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1777/152246) while in subpopulation AFR AF= 0.0408 (1697/41550). AF 95% confidence interval is 0.0392. There are 41 homozygotes in gnomad4. There are 842 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 41 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GHR | NM_000163.5 | c.785-9G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000230882.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GHR | ENST00000230882.9 | c.785-9G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000163.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0116 AC: 1762AN: 152128Hom.: 36 Cov.: 32
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GnomAD3 exomes AF: 0.00300 AC: 748AN: 249370Hom.: 17 AF XY: 0.00216 AC XY: 291AN XY: 134952
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GnomAD4 exome AF: 0.00107 AC: 1100AN: 1026030Hom.: 17 Cov.: 15 AF XY: 0.000890 AC XY: 472AN XY: 530252
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GnomAD4 genome AF: 0.0117 AC: 1777AN: 152246Hom.: 41 Cov.: 32 AF XY: 0.0113 AC XY: 842AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Laron-type isolated somatotropin defect Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 9
Find out detailed SpliceAI scores and Pangolin per-transcript scores at