Variant 5-42711178-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000230882.9(GHR):c.619-29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,581,668 control chromosomes in the GnomAD database, including 829 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.042 ( 186 hom., cov: 33)

Exomes 𝑓: 0.025 ( 643 hom. )

Consequence

GHR
ENST00000230882.9 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0820

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 -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 5-42711178-C-T is Benign according to our data. Variant chr5-42711178-C-T is described in ClinVar as [Benign]. Clinvar id is 255406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-42711178-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0811 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.619-29C>T		intron_variant		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.619-29C>T		intron_variant		1	NM_000163.5	ENSP00000230882	P1	P10912-1

Frequencies

GnomAD3 genomes

AF:

0.0423

AC:

6424

AN:

152010

Hom.:

186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0835

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0325

Gnomad ASJ

AF:

0.0397

Gnomad EAS

AF:

0.0191

Gnomad SAS

AF:

0.0247

Gnomad FIN

AF:

0.0142

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0268

Gnomad OTH

AF:

0.0430

GnomAD3 exomes

AF:

0.0281

AC:

7053

AN:

251004

Hom.:

155

AF XY:

0.0281

AC XY:

3811

AN XY:

135646

show subpopulations

Gnomad AFR exome

AF:

0.0837

Gnomad AMR exome

AF:

0.0187

Gnomad ASJ exome

AF:

0.0447

Gnomad EAS exome

AF:

0.0182

Gnomad SAS exome

AF:

0.0293

Gnomad FIN exome

AF:

0.0148

Gnomad NFE exome

AF:

0.0252

Gnomad OTH exome

AF:

0.0306

GnomAD4 exome

AF:

0.0253

AC:

36194

AN:

1429540

Hom.:

643

Cov.:

AF XY:

0.0256

AC XY:

18239

AN XY:

713208

show subpopulations

Gnomad4 AFR exome

AF:

0.0863

Gnomad4 AMR exome

AF:

0.0206

Gnomad4 ASJ exome

AF:

0.0462

Gnomad4 EAS exome

AF:

0.0238

Gnomad4 SAS exome

AF:

0.0288

Gnomad4 FIN exome

AF:

0.0148

Gnomad4 NFE exome

AF:

0.0230

Gnomad4 OTH exome

AF:

0.0293

GnomAD4 genome

AF:

0.0423

AC:

6431

AN:

152128

Hom.:

186

Cov.:

AF XY:

0.0407

AC XY:

3023

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0834

Gnomad4 AMR

AF:

0.0323

Gnomad4 ASJ

AF:

0.0397

Gnomad4 EAS

AF:

0.0191

Gnomad4 SAS

AF:

0.0247

Gnomad4 FIN

AF:

0.0142

Gnomad4 NFE

AF:

0.0268

Gnomad4 OTH

AF:

0.0425

Alfa

AF:

0.0343

Hom.:

Bravo

AF:

0.0447

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.63

BranchPoint Hunter

3.0

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