5-42718826-G-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000163.5(GHR):c.1319G>T(p.Cys440Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,614,006 control chromosomes in the GnomAD database, including 1,923 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000163.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0179 AC: 2724AN: 152050Hom.: 145 Cov.: 32
GnomAD3 exomes AF: 0.0404 AC: 10140AN: 251082Hom.: 729 AF XY: 0.0468 AC XY: 6356AN XY: 135710
GnomAD4 exome AF: 0.0230 AC: 33568AN: 1461840Hom.: 1779 Cov.: 34 AF XY: 0.0274 AC XY: 19923AN XY: 727232
GnomAD4 genome AF: 0.0179 AC: 2725AN: 152166Hom.: 144 Cov.: 32 AF XY: 0.0206 AC XY: 1531AN XY: 74404
ClinVar
Submissions by phenotype
not provided Benign:4
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This variant is associated with the following publications: (PMID: 8421103, 20981092, 10566675, 19344888) -
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not specified Benign:2
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Laron-type isolated somatotropin defect Benign:2
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. -
This variant is interpreted as a Benign - Stand Alone, for Laron syndrome, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at