chr5-42424601-A-T
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000163.5(GHR):c.-12+646A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00073 in 1,534,386 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.0039 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00038 ( 3 hom. )
Consequence
GHR
NM_000163.5 intron
NM_000163.5 intron
Scores
2
Splicing: ADA: 0.9199
2
Clinical Significance
Conservation
PhyloP100: 0.306
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 Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 5-42424601-A-T is Benign according to our data. Variant chr5-42424601-A-T is described in ClinVar as [Benign]. Clinvar id is 3035850.Status of the report is no_assertion_criteria_provided, 0 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00393 (598/152272) while in subpopulation AFR AF= 0.014 (580/41576). AF 95% confidence interval is 0.013. There are 4 homozygotes in gnomad4. There are 261 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 4 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GHR | NM_000163.5 | c.-12+646A>T | intron_variant | ENST00000230882.9 | |||
GHR | NM_001242399.2 | c.10+3A>T | splice_donor_region_variant, intron_variant | ||||
GHR | NM_001242400.2 | c.-297+3A>T | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GHR | ENST00000230882.9 | c.-12+646A>T | intron_variant | 1 | NM_000163.5 | P1 | |||
GHR | ENST00000615111.4 | c.-297+3A>T | splice_donor_region_variant, intron_variant | 5 | P1 | ||||
GHR | ENST00000620156.4 | c.10+3A>T | splice_donor_region_variant, intron_variant | 5 | |||||
GHR | ENST00000513671.5 | c.-12+3A>T | splice_donor_region_variant, intron_variant, NMD_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.00391 AC: 595AN: 152154Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.000749 AC: 96AN: 128114Hom.: 0 AF XY: 0.000585 AC XY: 41AN XY: 70142
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GnomAD4 exome AF: 0.000378 AC: 522AN: 1382114Hom.: 3 Cov.: 29 AF XY: 0.000315 AC XY: 215AN XY: 682058
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GnomAD4 genome AF: 0.00393 AC: 598AN: 152272Hom.: 4 Cov.: 32 AF XY: 0.00351 AC XY: 261AN XY: 74458
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
GHR-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 31, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -41
Find out detailed SpliceAI scores and Pangolin per-transcript scores at