7-30964079-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000823.4(GHRHR):c.11G>A(p.Arg4Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,550,576 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4W) has been classified as Uncertain significance.
Frequency
Consequence
NM_000823.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GHRHR | NM_000823.4 | c.11G>A | p.Arg4Gln | missense_variant | 1/13 | ENST00000326139.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GHRHR | ENST00000326139.7 | c.11G>A | p.Arg4Gln | missense_variant | 1/13 | 1 | NM_000823.4 | P1 | |
GHRHR | ENST00000466427.1 | n.285-4755G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000773 AC: 12AN: 155190Hom.: 0 AF XY: 0.0000612 AC XY: 5AN XY: 81760
GnomAD4 exome AF: 0.0000229 AC: 32AN: 1398228Hom.: 0 Cov.: 32 AF XY: 0.0000232 AC XY: 16AN XY: 689650
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152348Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74508
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 17, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 4 of the GHRHR protein (p.Arg4Gln). This variant is present in population databases (rs573168850, gnomAD 0.03%). This missense change has been observed in individual(s) with isolated growth hormone deficiency (PMID: 27501283). 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. Experimental studies have shown that this missense change does not substantially affect GHRHR function (PMID: 27501283). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at