5-42424171-AGTGTGTGTGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant names:

• chr5-42424171-AGT-A
• rs1158830359
• NM_000163.5:c.-12+263_-12+264delGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000163.5(GHR):​c.-12+263_-12+264delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (1171 hom., cov: 0)
• Consequence: GHR NM_000163.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHR	NM_000163.5	c.-12+263_-12+264delGT		intron_variant	Intron 1 of 9	ENST00000230882.9	NP_000154.1
GHR	NM_001242460.2	c.-12+263_-12+264delGT		intron_variant	Intron 1 of 8		NP_001229389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHR	ENST00000230882.9	c.-12+217_-12+218delGT		intron_variant	Intron 1 of 9	1	NM_000163.5	ENSP00000230882.4

Frequencies

GnomAD3 genomes AF: 0.161 AC: 16161 AN: 100072 Hom.: 1172 Cov.: 0

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.0727

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.161 AC: 16167 AN: 100140 Hom.: 1171 Cov.: 0 AF XY: 0.163 AC XY: 7578 AN XY: 46538

African (AFR) AF: 0.191 AC: 4607 AN: 24128

American (AMR) AF: 0.139 AC: 1430 AN: 10316

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 283 AN: 2652

East Asian (EAS) AF: 0.0339 AC: 109 AN: 3216

South Asian (SAS) AF: 0.0728 AC: 183 AN: 2514

European-Finnish (FIN) AF: 0.246 AC: 1209 AN: 4918

Middle Eastern (MID) AF: 0.174 AC: 33 AN: 190

European-Non Finnish (NFE) AF: 0.158 AC: 7934 AN: 50146

Other (OTH) AF: 0.154 AC: 211 AN: 1366

Alfa AF: 0.144 Hom.: 144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1158830359; hg19: chr5-42424273;