rs2972392

Positions:

• chr5-42495733-A-C

Variant summary

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

The NM_000163.5(GHR):​c.-11-70131A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,922 control chromosomes in the GnomAD database, including 15,267 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 0.44 (15267 hom., cov: 32)
• Consequence: GHR NM_000163.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GHR	NM_000163.5	c.-11-70131A>C		intron_variant		ENST00000230882.9	NP_000154.1
GHR	NM_001242399.2	c.11-70131A>C		intron_variant			NP_001229328.1
GHR	NM_001242400.2	c.-296-18347A>C		intron_variant			NP_001229329.1
GHR	NM_001242401.4	c.-12+12404A>C		intron_variant			NP_001229330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GHR	ENST00000230882.9	c.-11-70131A>C		intron_variant		1	NM_000163.5	ENSP00000230882.4
GHR	ENST00000620156.4	c.11-70131A>C		intron_variant		5		ENSP00000483403.1
GHR	ENST00000615111.4	c.-296-18347A>C		intron_variant		5		ENSP00000478291.1
GHR	ENST00000513671.5	n.-11-70131A>C		intron_variant		4		ENSP00000426739.1

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66934 AN: 151804 Hom.: 15261 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.441 AC: 66969 AN: 151922 Hom.: 15267 Cov.: 32 AF XY: 0.438 AC XY: 32497 AN XY: 74260

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.452

Alfa AF: 0.446 Hom.: 1909

Bravo AF: 0.445

Asia WGS AF: 0.250 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.6
DANN	Benign	0.46

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: rs2972392; hg19: chr5-42495835;