Variant 5-42629069-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate

The ENST00000230882.9(GHR):c.102G>C(p.Trp34Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000988 in 1,417,426 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 21)

Exomes 𝑓: 0.0000093 ( 1 hom. )

Consequence

GHR
ENST00000230882.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0770

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a topological_domain Extracellular (size 245) in uniprot entity GHR_HUMAN there are 52 pathogenic changes around while only 15 benign (78%) in ENST00000230882.9

BP4

Computational evidence support a benign effect (MetaRNN=0.18617094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GHR	NM_000163.5 linkuse as main transcript	c.102G>C	p.Trp34Cys	missense_variant	3/10	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.102G>C	p.Trp34Cys	missense_variant	3/10	1	NM_000163.5	ENSP00000230882	P1	P10912-1

Frequencies

GnomAD3 genomes

AF:

0.0000152

AC:

AN:

131430

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000321

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000933

AC:

AN:

1285996

Hom.:

Cov.:

AF XY:

0.00000777

AC XY:

AN XY:

643478

show subpopulations

Gnomad4 AFR exome

AF:

0.0000798

Gnomad4 AMR exome

AF:

0.0000473

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000825

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000152

AC:

AN:

131430

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64032

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000321

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.28

T;T;.;T;T;T;T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.86

.;.;D;.;.;D;.;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.19

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.0

N;N;.;N;N;N;N;.

MutationTaster

Benign

0.80

D;D;D

PrimateAI

Benign

0.25

PROVEAN

Benign

0.58

N;.;.;.;.;.;.;.

REVEL

Benign

0.17

Sift

Uncertain

0.014

D;.;.;.;.;.;.;.

Sift4G

Benign

0.18

T;T;T;T;T;T;T;T

Polyphen

0.18

B;B;.;B;B;B;B;.

Vest4

0.48

MutPred

0.43

Gain of catalytic residue at P33 (P = 0.0103);Gain of catalytic residue at P33 (P = 0.0103);.;Gain of catalytic residue at P33 (P = 0.0103);Gain of catalytic residue at P33 (P = 0.0103);Gain of catalytic residue at P33 (P = 0.0103);Gain of catalytic residue at P33 (P = 0.0103);Gain of catalytic residue at P33 (P = 0.0103);

MVP

0.82

MPC

0.086

ClinPred

0.099

GERP RS

2.4

Varity_R

0.11

gMVP

0.57

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over