chr5-42424598-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000163.5(GHR):c.-12+643G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
GHR
NM_000163.5 intron
NM_000163.5 intron
Scores
7
Splicing: ADA: 0.02141
2
Clinical Significance
Conservation
PhyloP100: 0.213
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.18665597).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GHR | NM_000163.5 | c.-12+643G>A | intron_variant | ENST00000230882.9 | |||
GHR | NM_001242399.2 | c.10G>A | p.Gly4Ser | missense_variant, splice_region_variant | 1/10 | ||
GHR | NM_001242400.2 | c.-297G>A | splice_region_variant, 5_prime_UTR_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GHR | ENST00000230882.9 | c.-12+643G>A | intron_variant | 1 | NM_000163.5 | P1 | |||
GHR | ENST00000620156.4 | c.10G>A | p.Gly4Ser | missense_variant, splice_region_variant | 1/10 | 5 | |||
GHR | ENST00000615111.4 | c.-297G>A | splice_region_variant, 5_prime_UTR_variant | 1/11 | 5 | P1 | |||
GHR | ENST00000513671.5 | c.-12G>A | splice_region_variant, 5_prime_UTR_variant, NMD_transcript_variant | 1/6 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Short stature due to partial GHR deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Dec 04, 2019 | This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,BP4. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MutationTaster
Benign
N;N
Vest4
MVP
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at