rs482204

Positions:

• chr3-172445039-G-A
• chr3-172445039-G-C
• chr3-172445039-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198407.2(GHSR):​c.*122C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,091,134 control chromosomes in the GnomAD database, including 281,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35419 hom., cov: 31)
  • Exomes 𝑓: 0.72 (245760 hom.)
• Consequence: GHSR NM_198407.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.60

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-172445039-G-A is Benign according to our data. Variant chr3-172445039-G-A is described in ClinVar as [Benign]. Clinvar id is 344196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GHSR	NM_198407.2	c.*122C>T		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.*122C>T		3_prime_UTR_variant	2/2	1	NM_198407.2	ENSP00000241256	P1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 102909 AN: 151570 Hom.: 35407 Cov.: 31

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.704

GnomAD4 exome AF: 0.720 AC: 676064 AN: 939446 Hom.: 245760 AF XY: 0.712 AC XY: 345791 AN XY: 485810

Gnomad4 AFR exome AF: 0.584

Gnomad4 AMR exome AF: 0.756

Gnomad4 ASJ exome AF: 0.696

Gnomad4 EAS exome AF: 0.661

Gnomad4 SAS exome AF: 0.517

Gnomad4 FIN exome AF: 0.698

Gnomad4 NFE exome AF: 0.751

Gnomad4 OTH exome AF: 0.709

GnomAD4 genome AF: 0.679 AC: 102972 AN: 151688 Hom.: 35419 Cov.: 31 AF XY: 0.674 AC XY: 50005 AN XY: 74146

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.705

Alfa AF: 0.664 Hom.: 4201

Bravo AF: 0.683

Asia WGS AF: 0.557 AC: 1941 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

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	-0.86
CADD	Benign	0.011
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs482204; hg19: chr3-172162829;