Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000163.5(GHR):c.785-9G>A variant causes a 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 (★★).
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]
Our verdict: Benign. The variant received -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 CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar as Benign. Clinvar id is 255408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42713420-G-A is described in CliVar 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 41 AR,Unknown,AD gene
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. -