chr5-42424171-A-AGTGT

Position:

• chr5-42424171-A-AGTGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000163.5(GHR):​c.-12+261_-12+264dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1209 hom., cov: 0)
• Consequence: GHR NM_000163.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21

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 -10 ACMG points.

• BP6: Variant 5-42424171-A-AGTGT is Benign according to our data. Variant chr5-42424171-A-AGTGT is described in ClinVar as [Benign]. Clinvar id is 1274890.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GHR	NM_000163.5	c.-12+261_-12+264dup		intron_variant		ENST00000230882.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHR	ENST00000230882.9	c.-12+261_-12+264dup		intron_variant		1	NM_000163.5	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 13068 AN: 100350 Hom.: 1212 Cov.: 0

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.0960

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.130 AC: 13075 AN: 100418 Hom.: 1209 Cov.: 0 AF XY: 0.132 AC XY: 6178 AN XY: 46682

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0883

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.128

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1158830359; hg19: chr5-42424273;