rs35683

chr3-10286566-A-Cchr3-10286566-A-G

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.334+138T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 594,828 control chromosomes in the GnomAD database, including 112,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (27934 hom., cov: 33)
  • Exomes 𝑓: 0.60 (84302 hom.)
• Consequence: GHRL NM_016362.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.794

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=-0.92).
• BP6: Variant 3-10286566-A-C is Benign according to our data. Variant chr3-10286566-A-C is described in ClinVar as [Benign]. Clinvar id is 1265406.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GHRL	NM_016362.5	c.334+138T>G		intron_variant		ENST00000335542.13
GHRLOS	NR_024145.2	n.397+713A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GHRL	ENST00000335542.13	c.334+138T>G		intron_variant		1	NM_016362.5	P4
GHRLOS	ENST00000439539.3	n.100+713A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90883 AN: 151986 Hom.: 27912 Cov.: 33

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.823

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.578

GnomAD4 exome AF: 0.600 AC: 265837 AN: 442724 Hom.: 84302 AF XY: 0.610 AC XY: 142269 AN XY: 233128

Gnomad4 AFR exome AF: 0.633

Gnomad4 AMR exome AF: 0.694

Gnomad4 ASJ exome AF: 0.578

Gnomad4 EAS exome AF: 0.985

Gnomad4 SAS exome AF: 0.811

Gnomad4 FIN exome AF: 0.562

Gnomad4 NFE exome AF: 0.521

Gnomad4 OTH exome AF: 0.585

GnomAD4 genome AF: 0.598 AC: 90957 AN: 152104 Hom.: 27934 Cov.: 33 AF XY: 0.608 AC XY: 45208 AN XY: 74360

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.976

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.578

Alfa AF: 0.533 Hom.: 22771

Bravo AF: 0.605

Asia WGS AF: 0.856 AC: 2976 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	-0.92
Cadd	Benign	0.67
Dann	Benign	0.65

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: rs35683; hg19: chr3-10328250;