rs562416

chr3-172444052-C-Achr3-172444052-C-Gchr3-172444052-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198407.2(GHSR):c.*1109G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,106 control chromosomes in the GnomAD database, including 50,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.81 (50530 hom., cov: 32)
• Consequence: GHSR NM_198407.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.305

Genes affected

GHSR (HGNC:4267): (growth hormone secretagogue receptor) This gene encodes a member of the G-protein coupled receptor family. The encoded protein may play a role in energy homeostasis and regulation of body weight. Two identified transcript variants are expressed in several tissues and are evolutionary conserved in fish and swine. One transcript, 1a, excises an intron and encodes the functional protein; this protein is the receptor for the Ghrelin ligand and defines a neuroendocrine pathway for growth hormone release. The second transcript (1b) retains the intron and does not function as a receptor for Ghrelin; however, it may function to attenuate activity of isoform 1a. Mutations in this gene are associated with autosomal idiopathic short stature.[provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-172444052-C-A is Benign according to our data. Variant chr3-172444052-C-A is described in ClinVar as [Benign]. Clinvar id is 344182.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GHSR	NM_198407.2	c.*1109G>T		3_prime_UTR_variant	2/2	ENST00000241256.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHSR	ENST00000241256.3	c.*1109G>T		3_prime_UTR_variant	2/2	1	NM_198407.2	P1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123132 AN: 151988 Hom.: 50505 Cov.: 32

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.816

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

GnomAD4 genome AF: 0.810 AC: 123207 AN: 152106 Hom.: 50530 Cov.: 32 AF XY: 0.816 AC XY: 60637 AN XY: 74354

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.859

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.923

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.819

Alfa AF: 0.787 Hom.: 2909

Bravo AF: 0.800

Asia WGS AF: 0.909 AC: 3153 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Short stature due to growth hormone secretagogue receptor deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.85
Dann	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs562416; hg19: chr3-172161842;