3-10287693-T-C

Variant names:

• chr3-10287693-T-C
• rs35681
• NM_016362.5:c.226-881A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016362.5(GHRL):​c.226-881A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,984 control chromosomes in the GnomAD database, including 25,152 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 0.57 (25152 hom., cov: 31)
• Consequence: GHRL NM_016362.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 23 publications found

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]

ENSG00000276678 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHRL	NM_016362.5	c.226-881A>G		intron_variant	Intron 4 of 5	ENST00000335542.13	NP_057446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRL	ENST00000335542.13	c.226-881A>G		intron_variant	Intron 4 of 5	1	NM_016362.5	ENSP00000335074.8

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86292 AN: 151864 Hom.: 25139 Cov.: 31

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.568 AC: 86352 AN: 151984 Hom.: 25152 Cov.: 31 AF XY: 0.578 AC XY: 42911 AN XY: 74256

African (AFR) AF: 0.553 AC: 22914 AN: 41454

American (AMR) AF: 0.649 AC: 9920 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2032 AN: 3466

East Asian (EAS) AF: 0.951 AC: 4904 AN: 5156

South Asian (SAS) AF: 0.777 AC: 3741 AN: 4816

European-Finnish (FIN) AF: 0.555 AC: 5842 AN: 10532

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35104 AN: 67968

Other (OTH) AF: 0.559 AC: 1181 AN: 2112

Alfa AF: 0.535 Hom.: 27077

Bravo AF: 0.572

Asia WGS AF: 0.810 AC: 2817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.72
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs35681; hg19: chr3-10329377;