5-42699942-A-G

Position:

chr5-42699942-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000163.5(GHR):c.558A>G(p.Gly186=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 1,596,728 control chromosomes in the GnomAD database, including 410,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 33294 hom., cov: 32)

Exomes 𝑓: 0.72 ( 377261 hom. )

Consequence

GHR
NM_000163.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.163

Variant links:

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]

GHR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 5-42699942-A-G is Benign according to our data. Variant chr5-42699942-A-G is described in ClinVar as [Benign]. Clinvar id is 198051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42699942-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.163 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GHR	NM_000163.5 linkuse as main transcript	c.558A>G	p.Gly186=	synonymous_variant	6/10	ENST00000230882.9	NP_000154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GHR	ENST00000230882.9 linkuse as main transcript	c.558A>G	p.Gly186=	synonymous_variant	6/10	1	NM_000163.5	ENSP00000230882	P1	P10912-1

Frequencies

GnomAD3 genomes

AF:

0.648

AC:

98504

AN:

151936

Hom.:

33283

Cov.:

show subpopulations

Gnomad AFR

AF:

0.443

Gnomad AMI

AF:

0.597

Gnomad AMR

AF:

0.738

Gnomad ASJ

AF:

0.702

Gnomad EAS

AF:

0.841

Gnomad SAS

AF:

0.685

Gnomad FIN

AF:

0.697

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.726

Gnomad OTH

AF:

0.644

GnomAD3 exomes

AF:

0.717

AC:

179881

AN:

250752

Hom.:

65631

AF XY:

0.715

AC XY:

96942

AN XY:

135498

show subpopulations

Gnomad AFR exome

AF:

0.435

Gnomad AMR exome

AF:

0.809

Gnomad ASJ exome

AF:

0.694

Gnomad EAS exome

AF:

0.848

Gnomad SAS exome

AF:

0.676

Gnomad FIN exome

AF:

0.694

Gnomad NFE exome

AF:

0.727

Gnomad OTH exome

AF:

0.707

GnomAD4 exome

AF:

0.720

AC:

1039709

AN:

1444674

Hom.:

377261

Cov.:

AF XY:

0.719

AC XY:

517201

AN XY:

719804

show subpopulations

Gnomad4 AFR exome

AF:

0.431

Gnomad4 AMR exome

AF:

0.799

Gnomad4 ASJ exome

AF:

0.697

Gnomad4 EAS exome

AF:

0.878

Gnomad4 SAS exome

AF:

0.678

Gnomad4 FIN exome

AF:

0.697

Gnomad4 NFE exome

AF:

0.726

Gnomad4 OTH exome

AF:

0.699

GnomAD4 genome

AF:

0.648

AC:

98533

AN:

152054

Hom.:

33294

Cov.:

AF XY:

0.652

AC XY:

48468

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.442

Gnomad4 AMR

AF:

0.738

Gnomad4 ASJ

AF:

0.702

Gnomad4 EAS

AF:

0.842

Gnomad4 SAS

AF:

0.686

Gnomad4 FIN

AF:

0.697

Gnomad4 NFE

AF:

0.726

Gnomad4 OTH

AF:

0.647

Alfa

AF:

0.699

Hom.:

27579

Bravo

AF:

0.642

Asia WGS

AF:

0.758

AC:

2637

AN:

3478

EpiCase

AF:

0.726

EpiControl

AF:

0.719

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 30, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Laron-type isolated somatotropin defect

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 29, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 21, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Short stature due to partial GHR deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.2

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over