5-42595009-C-T

Variant names:

• chr5-42595009-C-T
• rs28943882
• NM_000163.5:c.70+29065C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000163.5(GHR):​c.70+29065C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,830 control chromosomes in the GnomAD database, including 4,819 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 0.23 (4819 hom., cov: 32)
• Consequence: GHR NM_000163.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHR	NM_000163.5	c.70+29065C>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.70+29065C>T		intron_variant	Intron 2 of 9	1	NM_000163.5	ENSP00000230882.4

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35224 AN: 151708 Hom.: 4815 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0744

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.232 AC: 35247 AN: 151830 Hom.: 4819 Cov.: 32 AF XY: 0.231 AC XY: 17113 AN XY: 74194

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.0747

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.213

Alfa AF: 0.175 Hom.: 585

Bravo AF: 0.231

Asia WGS AF: 0.0600 AC: 212 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.45
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs28943882; hg19: chr5-42595111;