3-10291680-C-G

Position:

• chr3-10291680-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016362.5(GHRL):​c.-765-229G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,188 control chromosomes in the GnomAD database, including 5,561 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (5561 hom., cov: 33)
• Consequence: GHRL NM_016362.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GHRL	NM_016362.5	c.-765-229G>C		intron_variant		ENST00000335542.13	NP_057446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GHRL	ENST00000335542.13	c.-765-229G>C		intron_variant		1	NM_016362.5	ENSP00000335074.8

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35348 AN: 152070 Hom.: 5562 Cov.: 33

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.232 AC: 35348 AN: 152188 Hom.: 5561 Cov.: 33 AF XY: 0.245 AC XY: 18223 AN XY: 74396

Gnomad4 AFR AF: 0.0618

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.231

Alfa AF: 0.237 Hom.: 670

Bravo AF: 0.229

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.090
DANN	Benign	0.46

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: rs3755777; hg19: chr3-10333364;