chr7-30964121-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000823.4(GHRHR):c.53C>T(p.Pro18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,548,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P18P) has been classified as Likely benign.
Frequency
Consequence
NM_000823.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GHRHR | NM_000823.4 | c.53C>T | p.Pro18Leu | missense_variant | 1/13 | ENST00000326139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GHRHR | ENST00000326139.7 | c.53C>T | p.Pro18Leu | missense_variant | 1/13 | 1 | NM_000823.4 | P1 | |
GHRHR | ENST00000466427.1 | n.285-4713C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000237 AC: 36AN: 152184Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000182 AC: 28AN: 153766Hom.: 0 AF XY: 0.000173 AC XY: 14AN XY: 81130
GnomAD4 exome AF: 0.000203 AC: 284AN: 1396396Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 139AN XY: 688834
GnomAD4 genome AF: 0.000263 AC: 40AN: 152302Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74478
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 20, 2021 | This sequence change replaces proline with leucine at codon 18 of the GHRHR protein (p.Pro18Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs202243828, ExAC 0.05%). This missense change has been observed in individual(s) with isolated growth hormone deficiency (PMID: 18785993). This variant is also known as c.101C>T. ClinVar contains an entry for this variant (Variation ID: 1031665). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Isolated growth hormone deficiency type IB Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 11, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at