5-42424171-AGTGTGTGTGTGTGTGTGTGTGTGTGTGT-AGTGTGTGTGTGTGTGT

Variant names:

• chr5-42424171-AGTGTGTGTGTGT-A
• rs1158830359
• NM_000163.5:c.-12+253_-12+264delGTGTGTGTGTGT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000163.5(GHR):​c.-12+253_-12+264delGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (135 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: GHR NM_000163.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHR	NM_000163.5	c.-12+253_-12+264delGTGTGTGTGTGT		intron_variant	Intron 1 of 9	ENST00000230882.9	NP_000154.1
GHR	NM_001242460.2	c.-12+253_-12+264delGTGTGTGTGTGT		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+228delGTGTGTGTGTGT		intron_variant	Intron 1 of 9	1	NM_000163.5	ENSP00000230882.4

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 2394 AN: 100510 Hom.: 135 Cov.: 0

Gnomad AFR AF: 0.00700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.00226

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0659

Gnomad FIN AF: 0.0315

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00308

Gnomad OTH AF: 0.0297

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0239 AC: 2405 AN: 100578 Hom.: 135 Cov.: 0 AF XY: 0.0276 AC XY: 1292 AN XY: 46748

African (AFR) AF: 0.00714 AC: 173 AN: 24228

American (AMR) AF: 0.122 AC: 1259 AN: 10350

Ashkenazi Jewish (ASJ) AF: 0.00226 AC: 6 AN: 2658

East Asian (EAS) AF: 0.139 AC: 447 AN: 3218

South Asian (SAS) AF: 0.0655 AC: 165 AN: 2520

European-Finnish (FIN) AF: 0.0315 AC: 156 AN: 4950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 190

European-Non Finnish (NFE) AF: 0.00308 AC: 155 AN: 50396

Other (OTH) AF: 0.0321 AC: 44 AN: 1370

Alfa AF: 0.00 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

Splicing

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

Other links and lift over

dbSNP: rs1158830359; hg19: chr5-42424273;