chr5-42611746-T-G

Position:

• chr5-42611746-T-G

Variant summary

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

The NM_000163.5(GHR):​c.71-17292T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,168 control chromosomes in the GnomAD database, including 1,267 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 0.11 (1267 hom., cov: 32)
• Consequence: GHR NM_000163.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GHR	NM_000163.5	c.71-17292T>G		intron_variant		ENST00000230882.9	NP_000154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GHR	ENST00000230882.9	c.71-17292T>G		intron_variant		1	NM_000163.5	ENSP00000230882.4

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16309 AN: 152050 Hom.: 1266 Cov.: 32

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.0796

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0602

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.107 AC: 16305 AN: 152168 Hom.: 1267 Cov.: 32 AF XY: 0.109 AC XY: 8140 AN XY: 74390

Gnomad4 AFR AF: 0.0252

Gnomad4 AMR AF: 0.0982

Gnomad4 ASJ AF: 0.0796

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0603

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.111

Alfa AF: 0.119 Hom.: 662

Bravo AF: 0.0935

Asia WGS AF: 0.0250 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.53

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: rs13182117; hg19: chr5-42611848;