rs6887528

Variant names:

• chr5-42623450-C-T
• rs6887528
• NM_000163.5:c.71-5588C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000163.5(GHR):​c.71-5588C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.053 in 152,254 control chromosomes in the GnomAD database, including 266 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 0.053 (266 hom., cov: 32)
• Consequence: GHR NM_000163.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHR	NM_000163.5	c.71-5588C>T		intron_variant	Intron 2 of 9	ENST00000230882.9	NP_000154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHR	ENST00000230882.9	c.71-5588C>T		intron_variant	Intron 2 of 9	1	NM_000163.5	ENSP00000230882.4

Frequencies

GnomAD3 genomes AF: 0.0530 AC: 8061 AN: 152136 Hom.: 266 Cov.: 32

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0601

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0663

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0657

Gnomad OTH AF: 0.0740

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

GnomAD4 genome AF: 0.0530 AC: 8069 AN: 152254 Hom.: 266 Cov.: 32 AF XY: 0.0517 AC XY: 3852 AN XY: 74448

African (AFR) AF: 0.0369 AC: 1533 AN: 41542

American (AMR) AF: 0.0599 AC: 916 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5186

South Asian (SAS) AF: 0.0659 AC: 318 AN: 4824

European-Finnish (FIN) AF: 0.0280 AC: 297 AN: 10610

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0657 AC: 4467 AN: 68018

Other (OTH) AF: 0.0723 AC: 153 AN: 2116

Alfa AF: 0.0557 Hom.: 75

Bravo AF: 0.0542

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.091
DANN	Benign	0.21
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6887528; hg19: chr5-42623552;