3-172444137-C-G

Position:

• chr3-172444137-C-G

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.*1024G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0416 in 152,206 control chromosomes in the GnomAD database, including 225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.042 (225 hom., cov: 33)
• Consequence: GHSR NM_198407.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.804

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=-0.84).
• BP6: Variant 3-172444137-C-G is Benign according to our data. Variant chr3-172444137-C-G is described in ClinVar as [Benign]. Clinvar id is 344184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GHSR	NM_198407.2	c.*1024G>C		3_prime_UTR_variant	2/2	ENST00000241256.3	NP_940799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GHSR	ENST00000241256.3	c.*1024G>C		3_prime_UTR_variant	2/2	1	NM_198407.2	ENSP00000241256	P1

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6312 AN: 152088 Hom.: 224 Cov.: 33

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0412

Gnomad FIN AF: 0.00848

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0417

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

GnomAD4 genome AF: 0.0416 AC: 6327 AN: 152206 Hom.: 225 Cov.: 33 AF XY: 0.0409 AC XY: 3040 AN XY: 74418

Gnomad4 AFR AF: 0.0863

Gnomad4 AMR AF: 0.0254

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.0408

Gnomad4 FIN AF: 0.00848

Gnomad4 NFE AF: 0.0275

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0364 Hom.: 27

Bravo AF: 0.0443

Asia WGS AF: 0.0250 AC: 86 AN: 3478

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 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	-0.84
CADD	Benign	0.42
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9880206; hg19: chr3-172161927;