ENST00000466427.1:n.285-5536C>T

Variant names:

• chr7-30963298-C-T
• rs17159772
• ENST00000466427.1:n.285-5536C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000466427.1(GHRHR):​n.285-5536C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,960 control chromosomes in the GnomAD database, including 6,657 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 0.29 (6657 hom., cov: 32)
• Consequence: GHRHR ENST00000466427.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• Publications: 3 publications found

Genes affected

GHRHR (HGNC:4266): (growth hormone releasing hormone receptor) This gene encodes a receptor for growth hormone-releasing hormone. Binding of this hormone to the receptor leads to synthesis and release of growth hormone. Mutations in this gene have been associated with isolated growth hormone deficiency (IGHD), also known as Dwarfism of Sindh, a disorder characterized by short stature. [provided by RefSeq, Jun 2010]

GHRHR Gene-Disease associations (from GenCC):

• isolated growth hormone deficiency type IB

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet
• isolated growth hormone deficiency, type 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRHR	ENST00000466427.1	n.285-5536C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44258 AN: 151842 Hom.: 6651 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0819

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.291 AC: 44276 AN: 151960 Hom.: 6657 Cov.: 32 AF XY: 0.287 AC XY: 21300 AN XY: 74278

African (AFR) AF: 0.319 AC: 13216 AN: 41426

American (AMR) AF: 0.222 AC: 3393 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 930 AN: 3468

East Asian (EAS) AF: 0.0815 AC: 422 AN: 5178

South Asian (SAS) AF: 0.315 AC: 1513 AN: 4806

European-Finnish (FIN) AF: 0.249 AC: 2623 AN: 10538

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21185 AN: 67964

Other (OTH) AF: 0.291 AC: 613 AN: 2110

Alfa AF: 0.287 Hom.: 2046

Bravo AF: 0.287

Asia WGS AF: 0.248 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-0.53

Splicing

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

Other links and lift over

dbSNP: rs17159772; hg19: chr7-31002913;