Variant 5-42713407-G-A 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 NM_000163.5(GHR):c.785-22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,059,712 control chromosomes in the GnomAD database, including 274 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 135 hom., cov: 32)

Exomes 𝑓: 0.010 ( 139 hom. )

Consequence

GHR
NM_000163.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.271

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

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-42713407-G-A is Benign according to our data. Variant chr5-42713407-G-A is described in ClinVar as [Benign]. Clinvar id is 255407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GHR	NM_000163.5 linkuse as main transcript	c.785-22G>A		intron_variant		ENST00000230882.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHR	ENST00000230882.9 linkuse as main transcript	c.785-22G>A		intron_variant		1	NM_000163.5	P1	P10912-1

Frequencies

GnomAD3 genomes

AF:

0.0264

AC:

4016

AN:

152082

Hom.:

135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0770

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00747

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.00736

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00744

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.0119

AC:

2965

AN:

248640

Hom.:

AF XY:

0.0111

AC XY:

1500

AN XY:

134624

show subpopulations

Gnomad AFR exome

AF:

0.0780

Gnomad AMR exome

AF:

0.00342

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.00632

Gnomad NFE exome

AF:

0.00809

Gnomad OTH exome

AF:

0.0100

GnomAD4 exome

AF:

0.0102

AC:

9238

AN:

907512

Hom.:

139

Cov.:

AF XY:

0.0101

AC XY:

4786

AN XY:

475290

show subpopulations

Gnomad4 AFR exome

AF:

0.0808

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.00445

Gnomad4 EAS exome

AF:

0.000216

Gnomad4 SAS exome

AF:

0.0138

Gnomad4 FIN exome

AF:

0.00802

Gnomad4 NFE exome

AF:

0.00842

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.0264

AC:

4024

AN:

152200

Hom.:

135

Cov.:

AF XY:

0.0250

AC XY:

1859

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0770

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0137

Gnomad4 FIN

AF:

0.00736

Gnomad4 NFE

AF:

0.00744

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.0162

Hom.:

Bravo

AF:

0.0281

Asia WGS

AF:

0.0150

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.8

DANN

Benign

0.68

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