rs2940920

Positions:

• chr5-42471497-T-C

Variant summary

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

The NM_000163.5(GHR):​c.-12+47542T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,224 control chromosomes in the GnomAD database, including 2,542 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 (2542 hom., cov: 32)
• Consequence: GHR NM_000163.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GHR	NM_000163.5	c.-12+47542T>C		intron_variant		ENST00000230882.9
GHR	NM_001242399.2	c.10+46899T>C		intron_variant
GHR	NM_001242400.2	c.-296-42583T>C		intron_variant
GHR	NM_001242401.4	c.-104-11740T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHR	ENST00000230882.9	c.-12+47542T>C		intron_variant		1	NM_000163.5	P1
GHR	ENST00000615111.4	c.-296-42583T>C		intron_variant		5		P1
GHR	ENST00000620156.4	c.10+46899T>C		intron_variant		5
GHR	ENST00000513671.5	c.-12+46899T>C		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26377 AN: 152106 Hom.: 2541 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0756

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.173 AC: 26379 AN: 152224 Hom.: 2542 Cov.: 32 AF XY: 0.166 AC XY: 12391 AN XY: 74442

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0756

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.184

Alfa AF: 0.175 Hom.: 318

Bravo AF: 0.181

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.51
DANN	Benign	0.56

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: rs2940920; hg19: chr5-42471599;