NM_198407.2:c.*834C>A

Variant names:

• chr3-172444327-G-T
• rs565105
• NM_198407.2:c.*834C>A

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.*834C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,010 control chromosomes in the GnomAD database, including 35,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (35541 hom., cov: 32)
• Consequence: GHSR NM_198407.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.62

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=-0.88).
• BP6: Variant 3-172444327-G-T is Benign according to our data. Variant chr3-172444327-G-T is described in ClinVar as [Benign]. Clinvar id is 344186.Status of the report is criteria_provided_single_submitter, 1 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 rank	MANE	Protein	UniProt
GHSR	NM_198407.2	c.*834C>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000241256.3	NP_940799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHSR	ENST00000241256	c.*834C>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_198407.2	ENSP00000241256.2

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103179 AN: 151892 Hom.: 35532 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.679 AC: 103239 AN: 152010 Hom.: 35541 Cov.: 32 AF XY: 0.675 AC XY: 50118 AN XY: 74284

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.705

Alfa AF: 0.729 Hom.: 63075

Bravo AF: 0.683

Asia WGS AF: 0.556 AC: 1935 AN: 3474

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

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs565105; hg19: chr3-172162117;