rs495225

chr3-172448243-G-Achr3-172448243-G-Cchr3-172448243-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_198407.2(GHSR):c.171C>T(p.Gly57=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 1,613,588 control chromosomes in the GnomAD database, including 384,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (31186 hom., cov: 33)
  • Exomes 𝑓: 0.69 (353194 hom.)
• Consequence: GHSR NM_198407.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.642

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 -16 ACMG points.

• BP6: Variant 3-172448243-G-A is Benign according to our data. Variant chr3-172448243-G-A is described in ClinVar as [Benign]. Clinvar id is 263109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-172448243-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GHSR	NM_198407.2	c.171C>T	p.Gly57=	synonymous_variant	1/2	ENST00000241256.3
GHSR	NM_004122.2	c.171C>T	p.Gly57=	synonymous_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHSR	ENST00000241256.3	c.171C>T	p.Gly57=	synonymous_variant	1/2	1	NM_198407.2	P1
GHSR	ENST00000427970.1	c.171C>T	p.Gly57=	synonymous_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95803 AN: 152044 Hom.: 31184 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.656

GnomAD3 exomes AF: 0.662 AC: 164382 AN: 248238 Hom.: 55941 AF XY: 0.655 AC XY: 88132 AN XY: 134598

Gnomad AFR exome AF: 0.464

Gnomad AMR exome AF: 0.753

Gnomad ASJ exome AF: 0.663

Gnomad EAS exome AF: 0.642

Gnomad SAS exome AF: 0.454

Gnomad FIN exome AF: 0.683

Gnomad NFE exome AF: 0.719

Gnomad OTH exome AF: 0.665

GnomAD4 exome AF: 0.691 AC: 1009895 AN: 1461426 Hom.: 353194 Cov.: 78 AF XY: 0.685 AC XY: 498089 AN XY: 726986

Gnomad4 AFR exome AF: 0.455

Gnomad4 AMR exome AF: 0.739

Gnomad4 ASJ exome AF: 0.663

Gnomad4 EAS exome AF: 0.658

Gnomad4 SAS exome AF: 0.462

Gnomad4 FIN exome AF: 0.687

Gnomad4 NFE exome AF: 0.717

Gnomad4 OTH exome AF: 0.670

GnomAD4 genome AF: 0.630 AC: 95837 AN: 152162 Hom.: 31186 Cov.: 33 AF XY: 0.627 AC XY: 46615 AN XY: 74382

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.658

Alfa AF: 0.697 Hom.: 39704

Bravo AF: 0.630

Asia WGS AF: 0.526 AC: 1836 AN: 3478

EpiCase AF: 0.701

EpiControl AF: 0.716

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 05, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Short stature due to growth hormone secretagogue receptor deficiency Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	16
Dann	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.29		Position offset: 6

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

Publications

LitVar

Other links and lift over

dbSNP: rs495225; hg19: chr3-172166033; COSMIC: COSV53837352;