rs7732059

Variant names:

• chr5-42423370-G-C
• rs7732059
• NM_000163.5:c.-597G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-42423370-G-C
• chr5-42423370-G-T

Variant summary

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

The NM_000163.5(GHR):​c.-597G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,070 control chromosomes in the GnomAD database, including 5,036 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 0.25 (5036 hom., cov: 32)
• Consequence: GHR NM_000163.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHR	NM_000163.5	c.-597G>C		upstream_gene_variant		ENST00000230882.9	NP_000154.1
GHR	NM_001242460.2	c.-597G>C		upstream_gene_variant			NP_001229389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHR	ENST00000230882.9	c.-597G>C		upstream_gene_variant		1	NM_000163.5	ENSP00000230882.4

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37594 AN: 151952 Hom.: 5042 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.247 AC: 37592 AN: 152070 Hom.: 5036 Cov.: 32 AF XY: 0.246 AC XY: 18285 AN XY: 74336

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.250

Alfa AF: 0.156 Hom.: 342

Bravo AF: 0.238

Asia WGS AF: 0.0850 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7732059; hg19: chr5-42423472;