3-172448243-G-A

Position:

chr3-172448243-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000241256.3(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
ENST00000241256.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.642

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
GHSR	NM_198407.2 linkuse as main transcript	c.171C>T	p.Gly57=	synonymous_variant	1/2	ENST00000241256.3	NP_940799.1
GHSR	NM_004122.2 linkuse as main transcript	c.171C>T	p.Gly57=	synonymous_variant	1/1		NP_004113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GHSR	ENST00000241256.3 linkuse as main transcript	c.171C>T	p.Gly57=	synonymous_variant	1/2	1	NM_198407.2	ENSP00000241256	P1	Q92847-1
GHSR	ENST00000427970.1 linkuse as main transcript	c.171C>T	p.Gly57=	synonymous_variant	1/1			ENSP00000395344		Q92847-2

Frequencies

GnomAD3 genomes

AF:

0.630

AC:

95803

AN:

152044

Hom.:

31184

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.685

AC XY:

498089

AN XY:

726986

show subpopulations

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.:

AF XY:

0.627

AC XY:

46615

AN XY:

74382

show subpopulations

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:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 specified

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over