dbSNP rs33939197: GHR:c.-11-69908T>C (chr5-42495956-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000163.5(GHR):c.-11-69908T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,142 control chromosomes in the GnomAD database, including 2,810 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2810 hom., cov: 32)

Consequence

GHR
NM_000163.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.888

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

Laron syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
short stature due to partial GHR deficiency
Inheritance: Unknown, AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

GHR links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHR	NM_000163.5 link	c.-11-69908T>C		intron_variant	Intron 1 of 9	ENST00000230882.9	NP_000154.1	P10912-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GHR	ENST00000230882.9 link	c.-11-69908T>C	intron_variant	Intron 1 of 9	1	NM_000163.5	ENSP00000230882.4	P10912-1
GHR	ENST00000620156.4 link	c.11-69908T>C	intron_variant	Intron 1 of 9	5		ENSP00000483403.1	A0A087X0H5
GHR	ENST00000615111.4 link	c.-296-18124T>C	intron_variant	Intron 1 of 10	5		ENSP00000478291.1	P10912-1
GHR	ENST00000513671.5 link	n.-11-69908T>C	intron_variant	Intron 1 of 5	4		ENSP00000426739.1	E9PCN7

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27469

AN:

152024

Hom.:

2806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0774

Gnomad FIN

AF:

0.312

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.181

AC:

27474

AN:

152142

Hom.:

2810

Cov.:

AF XY:

0.182

AC XY:

13546

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.133

AC:

5511

AN:

41532

American (AMR)

AF:

0.162

AC:

2473

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

533

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5184

South Asian (SAS)

AF:

0.0777

AC:

375

AN:

4826

European-Finnish (FIN)

AF:

0.312

AC:

3299

AN:

10580

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.215

AC:

14618

AN:

67950

Other (OTH)

AF:

0.189

AC:

398

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1124

2248

3371

4495

5619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.204

Hom.:

456

Bravo

AF:

0.168

Asia WGS

AF:

0.0460

AC:

162

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

0.89

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over