rs2075356

chr3-10287125-T-C

Variant summary

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

The NM_016362.5(GHRL):c.226-313A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 199,714 control chromosomes in the GnomAD database, including 1,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.087 (808 hom., cov: 33)
  • Exomes 𝑓: 0.11 (353 hom.)
• Consequence: GHRL NM_016362.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.195

Genes affected

GHRL (HGNC:18129): (ghrelin and obestatin prepropeptide) This gene encodes the ghrelin-obestatin preproprotein that is cleaved to yield two peptides, ghrelin and obestatin. Ghrelin is a powerful appetite stimulant and plays an important role in energy homeostasis. Its secretion is initiated when the stomach is empty, whereupon it binds to the growth hormone secretagogue receptor in the hypothalamus which results in the secretion of growth hormone (somatotropin). Ghrelin is thought to regulate multiple activities, including hunger, reward perception via the mesolimbic pathway, gastric acid secretion, gastrointestinal motility, and pancreatic glucose-stimulated insulin secretion. It was initially proposed that obestatin plays an opposing role to ghrelin by promoting satiety and thus decreasing food intake, but this action is still debated. Recent reports suggest multiple metabolic roles for obestatin, including regulating adipocyte function and glucose metabolism. Alternative splicing results in multiple transcript variants. In addition, antisense transcripts for this gene have been identified and may potentially regulate ghrelin-obestatin preproprotein expression. [provided by RefSeq, Nov 2014]

GHRLOS (HGNC:33885): (ghrelin opposite strand/antisense RNA) This gene is an antisense gene of the ghrelin/obestatin prepropeptide gene. Alternatively spliced transcript variants have been identified and they may function as non-coding regulatory RNAs. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-10287125-T-C is Benign according to our data. Variant chr3-10287125-T-C is described in ClinVar as [Benign]. Clinvar id is 1263639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GHRL	NM_016362.5	c.226-313A>G		intron_variant		ENST00000335542.13
GHRLOS	NR_024145.2	n.398-820T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHRL	ENST00000335542.13	c.226-313A>G		intron_variant		1	NM_016362.5	P4
GHRLOS	ENST00000439539.3	n.101-289T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13210 AN: 152156 Hom.: 807 Cov.: 33

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0976

Gnomad OTH AF: 0.0879

GnomAD4 exome AF: 0.108 AC: 5143 AN: 47440 Hom.: 353 Cov.: 0 AF XY: 0.111 AC XY: 2780 AN XY: 25150

Gnomad4 AFR exome AF: 0.0232

Gnomad4 AMR exome AF: 0.0830

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.128

Gnomad4 NFE exome AF: 0.0960

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.0867 AC: 13204 AN: 152274 Hom.: 808 Cov.: 33 AF XY: 0.0899 AC XY: 6694 AN XY: 74442

Gnomad4 AFR AF: 0.0257

Gnomad4 AMR AF: 0.0791

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0975

Gnomad4 OTH AF: 0.0884

Alfa AF: 0.0818 Hom.: 67

Bravo AF: 0.0771

Asia WGS AF: 0.174 AC: 605 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.5
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2075356; hg19: chr3-10328809; COSMIC: COSV55055123; COSMIC: COSV55055123;