rs2972416

Positions:

• chr5-42474627-C-A
• chr5-42474627-C-T

Variant summary

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

The NM_000163.5(GHR):​c.-12+50672C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 151,522 control chromosomes in the GnomAD database, including 2,301 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 0.17 (2301 hom., cov: 31)
• Consequence: GHR NM_000163.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GHR	NM_000163.5	c.-12+50672C>A		intron_variant		ENST00000230882.9	NP_000154.1
GHR	NM_001242399.2	c.10+50029C>A		intron_variant			NP_001229328.1
GHR	NM_001242400.2	c.-296-39453C>A		intron_variant			NP_001229329.1
GHR	NM_001242401.4	c.-104-8610C>A		intron_variant			NP_001229330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GHR	ENST00000230882.9	c.-12+50672C>A		intron_variant		1	NM_000163.5	ENSP00000230882.4
GHR	ENST00000620156.4	c.10+50029C>A		intron_variant		5		ENSP00000483403.1
GHR	ENST00000615111.4	c.-296-39453C>A		intron_variant		5		ENSP00000478291.1
GHR	ENST00000513671.5	n.-12+50029C>A		intron_variant		4		ENSP00000426739.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25086 AN: 151404 Hom.: 2301 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.00252

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0817

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.166 AC: 25084 AN: 151522 Hom.: 2301 Cov.: 31 AF XY: 0.160 AC XY: 11836 AN XY: 74026

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.00252

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.0817

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.178

Alfa AF: 0.0401 Hom.: 37

Bravo AF: 0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.075
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: rs2972416; hg19: chr5-42474729; COSMIC: COSV50113967;