3-172447967-G-C

Position:

chr3-172447967-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_198407.2(GHSR):c.447C>G(p.Leu149Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 1,614,016 control chromosomes in the GnomAD database, including 918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 159 hom., cov: 32)

Exomes 𝑓: 0.028 ( 759 hom. )

Consequence

GHSR
NM_198407.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.207

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 3-172447967-G-C is Benign according to our data. Variant chr3-172447967-G-C is described in ClinVar as [Benign]. Clinvar id is 344200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-172447967-G-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.207 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GHSR	NM_198407.2 link	c.447C>G	p.Leu149Leu	synonymous_variant	1/2	ENST00000241256.3	NP_940799.1	Q92847-1
GHSR	NM_004122.2 link	c.447C>G	p.Leu149Leu	synonymous_variant	1/1		NP_004113.1	Q92847-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GHSR	ENST00000241256.3 link	c.447C>G	p.Leu149Leu	synonymous_variant	1/2	1	NM_198407.2	ENSP00000241256.2		Q92847-1
GHSR	ENST00000427970.1 link	c.447C>G	p.Leu149Leu	synonymous_variant	1/1	6		ENSP00000395344.1		Q92847-2

Frequencies

GnomAD3 genomes

AF:

0.0360

AC:

5473

AN:

152212

Hom.:

158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0669

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0233

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0406

Gnomad FIN

AF:

0.00837

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0274

Gnomad OTH

AF:

0.0388

GnomAD3 exomes

AF:

0.0277

AC:

6955

AN:

250954

Hom.:

153

AF XY:

0.0286

AC XY:

3887

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.0680

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.0322

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0470

Gnomad FIN exome

AF:

0.00861

Gnomad NFE exome

AF:

0.0284

Gnomad OTH exome

AF:

0.0328

GnomAD4 exome

AF:

0.0279

AC:

40838

AN:

1461686

Hom.:

759

Cov.:

AF XY:

0.0284

AC XY:

20659

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.0715

Gnomad4 AMR exome

AF:

0.0154

Gnomad4 ASJ exome

AF:

0.0326

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.0485

Gnomad4 FIN exome

AF:

0.00908

Gnomad4 NFE exome

AF:

0.0269

Gnomad4 OTH exome

AF:

0.0319

GnomAD4 genome

AF:

0.0360

AC:

5477

AN:

152330

Hom.:

159

Cov.:

AF XY:

0.0353

AC XY:

2630

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0668

Gnomad4 AMR

AF:

0.0232

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0406

Gnomad4 FIN

AF:

0.00837

Gnomad4 NFE

AF:

0.0274

Gnomad4 OTH

AF:

0.0384

Alfa

AF:

0.0228

Hom.:

Bravo

AF:

0.0379

EpiCase

AF:

0.0276

EpiControl

AF:

0.0285

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2020	- -

Short stature due to growth hormone secretagogue receptor deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

-0.62

CADD

Benign

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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