rs509035

Positions:

• chr3-172445659-G-A
• chr3-172445659-G-C
• chr3-172445659-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000241256.3(GHSR):​c.797-194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,096 control chromosomes in the GnomAD database, including 5,693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5693 hom., cov: 32)
• Consequence: GHSR ENST00000241256.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0900

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=-0.81).
• BP6: Variant 3-172445659-G-A is Benign according to our data. Variant chr3-172445659-G-A is described in ClinVar as [Benign]. Clinvar id is 1222463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GHSR	NM_198407.2	c.797-194C>T		intron_variant		ENST00000241256.3	NP_940799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GHSR	ENST00000241256.3	c.797-194C>T		intron_variant		1	NM_198407.2	ENSP00000241256	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37933 AN: 151978 Hom.: 5684 Cov.: 32

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.250 AC: 37954 AN: 152096 Hom.: 5693 Cov.: 32 AF XY: 0.253 AC XY: 18804 AN XY: 74328

Gnomad4 AFR AF: 0.0836

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.242

Alfa AF: 0.292 Hom.: 12125

Bravo AF: 0.246

Asia WGS AF: 0.319 AC: 1112 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs509035; hg19: chr3-172163449;