3-10290784-C-T

Variant names:

• chr3-10290784-C-T
• rs27647
• NM_016362.5:c.-98G>A

Variant summary

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

The NM_016362.5(GHRL):​c.-98G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 989,806 control chromosomes in the GnomAD database, including 190,567 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 0.68 (35417 hom., cov: 32)
  • Exomes 𝑓: 0.61 (155150 hom.)
• Consequence: GHRL NM_016362.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 56 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016362.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRL	NM_016362.5	MANE Select	c.-98G>A		5_prime_UTR	Exon 2 of 6	NP_057446.1
	GHRL	NM_001302821.2		c.-98G>A		5_prime_UTR	Exon 3 of 7	NP_001289750.1
	GHRL	NM_001302822.2		c.-98G>A		5_prime_UTR	Exon 2 of 6	NP_001289751.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRL	ENST00000335542.13	TSL:1 MANE Select	c.-98G>A		5_prime_UTR	Exon 2 of 6	ENSP00000335074.8
	GHRL	ENST00000429122.1	TSL:1	c.-98G>A		5_prime_UTR	Exon 2 of 6	ENSP00000414819.1
	GHRL	ENST00000457360.5	TSL:1	c.-98G>A		5_prime_UTR	Exon 2 of 6	ENSP00000391406.1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102585 AN: 151972 Hom.: 35392 Cov.: 32

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.657

GnomAD4 exome AF: 0.606 AC: 507727 AN: 837716 Hom.: 155150 Cov.: 25 AF XY: 0.606 AC XY: 234549 AN XY: 387116

African (AFR) AF: 0.757 AC: 12036 AN: 15906

American (AMR) AF: 0.778 AC: 874 AN: 1124

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 3026 AN: 5284

East Asian (EAS) AF: 0.918 AC: 3712 AN: 4044

South Asian (SAS) AF: 0.862 AC: 14229 AN: 16510

European-Finnish (FIN) AF: 0.590 AC: 509 AN: 862

Middle Eastern (MID) AF: 0.695 AC: 1139 AN: 1638

European-Non Finnish (NFE) AF: 0.594 AC: 454554 AN: 764780

Other (OTH) AF: 0.640 AC: 17648 AN: 27568

GnomAD4 genome AF: 0.675 AC: 102663 AN: 152090 Hom.: 35417 Cov.: 32 AF XY: 0.682 AC XY: 50734 AN XY: 74352

African (AFR) AF: 0.753 AC: 31246 AN: 41468

American (AMR) AF: 0.755 AC: 11538 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2035 AN: 3470

East Asian (EAS) AF: 0.906 AC: 4691 AN: 5180

South Asian (SAS) AF: 0.879 AC: 4243 AN: 4826

European-Finnish (FIN) AF: 0.607 AC: 6412 AN: 10572

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40366 AN: 67968

Other (OTH) AF: 0.654 AC: 1383 AN: 2114

Alfa AF: 0.651 Hom.: 13958

Bravo AF: 0.685

Asia WGS AF: 0.856 AC: 2977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.2
DANN	Benign	0.80
PhyloP100		-0.27
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs27647; hg19: chr3-10332468; COSMIC: COSV55055880; COSMIC: COSV55055880;