rs495225

Variant names:

• chr3-172448243-G-A
• rs495225
• NM_198407.2:c.171C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-172448243-G-A
• chr3-172448243-G-C
• chr3-172448243-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_198407.2(GHSR):​c.171C>T​(p.Gly57Gly) 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:6
• Conservation: PhyloP100: 0.642
• Publications: 36 publications found

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]

GHSR Gene-Disease associations (from GenCC):

• short stature due to GHSR deficiency

  Inheritance: AD, SD, AR Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 263109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
GHSR	NM_198407.2	c.171C>T	p.Gly57Gly	synonymous_variant	Exon 1 of 2	ENST00000241256.3	NP_940799.1
GHSR	NM_004122.2	c.171C>T	p.Gly57Gly	synonymous_variant	Exon 1 of 1		NP_004113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHSR	ENST00000241256.3	c.171C>T	p.Gly57Gly	synonymous_variant	Exon 1 of 2	1	NM_198407.2	ENSP00000241256.2
GHSR	ENST00000427970.1	c.171C>T	p.Gly57Gly	synonymous_variant	Exon 1 of 1	6		ENSP00000395344.1

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

GnomAD2 exomes AF: 0.662 AC: 164382 AN: 248238 AF XY: 0.655

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 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

African (AFR) AF: 0.455 AC: 15233 AN: 33480

American (AMR) AF: 0.739 AC: 33022 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 17335 AN: 26134

East Asian (EAS) AF: 0.658 AC: 26138 AN: 39694

South Asian (SAS) AF: 0.462 AC: 39876 AN: 86250

European-Finnish (FIN) AF: 0.687 AC: 36464 AN: 53048

Middle Eastern (MID) AF: 0.649 AC: 3740 AN: 5766

European-Non Finnish (NFE) AF: 0.717 AC: 797613 AN: 1111958

Other (OTH) AF: 0.670 AC: 40474 AN: 60390

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

African (AFR) AF: 0.464 AC: 19271 AN: 41516

American (AMR) AF: 0.689 AC: 10542 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2286 AN: 3470

East Asian (EAS) AF: 0.639 AC: 3295 AN: 5160

South Asian (SAS) AF: 0.458 AC: 2209 AN: 4824

European-Finnish (FIN) AF: 0.688 AC: 7285 AN: 10592

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48731 AN: 67982

Other (OTH) AF: 0.658 AC: 1390 AN: 2114

Alfa AF: 0.687 Hom.: 55605

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:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Aug 05, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.80
PhyloP100		0.64
PromoterAI		0.00020	Neutral
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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