ENST00000439539.3:n.596G>A

Variant names:

• chr3-10292337-G-A
• rs27498
• ENST00000439539.3:n.596G>A

Variant summary

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

The ENST00000439539.3(GHRLOS):​n.596G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 158,006 control chromosomes in the GnomAD database, including 16,334 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 0.44 (15802 hom., cov: 32)
  • Exomes 𝑓: 0.41 (532 hom.)
• Consequence: GHRLOS ENST00000439539.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 11 publications found

Genes affected

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]

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]

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 = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHRL	NM_016362.5	c.-766+505C>T		intron_variant	Intron 1 of 5	ENST00000335542.13	NP_057446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRL	ENST00000335542.13	c.-766+505C>T		intron_variant	Intron 1 of 5	1	NM_016362.5	ENSP00000335074.8

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66535 AN: 151900 Hom.: 15791 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.423

GnomAD4 exome AF: 0.408 AC: 2446 AN: 5988 Hom.: 532 Cov.: 0 AF XY: 0.423 AC XY: 1361 AN XY: 3220

African (AFR) AF: 0.421 AC: 16 AN: 38

American (AMR) AF: 0.583 AC: 28 AN: 48

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 60 AN: 140

East Asian (EAS) AF: 1.00 AC: 32 AN: 32

South Asian (SAS) AF: 0.551 AC: 527 AN: 956

European-Finnish (FIN) AF: 0.384 AC: 96 AN: 250

Middle Eastern (MID) AF: 0.375 AC: 12 AN: 32

European-Non Finnish (NFE) AF: 0.367 AC: 1491 AN: 4066

Other (OTH) AF: 0.432 AC: 184 AN: 426

GnomAD4 genome AF: 0.438 AC: 66575 AN: 152018 Hom.: 15802 Cov.: 32 AF XY: 0.450 AC XY: 33453 AN XY: 74292

African (AFR) AF: 0.410 AC: 17009 AN: 41464

American (AMR) AF: 0.554 AC: 8459 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1558 AN: 3468

East Asian (EAS) AF: 0.949 AC: 4905 AN: 5166

South Asian (SAS) AF: 0.593 AC: 2860 AN: 4822

European-Finnish (FIN) AF: 0.473 AC: 4985 AN: 10534

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25457 AN: 67980

Other (OTH) AF: 0.425 AC: 896 AN: 2108

Alfa AF: 0.407 Hom.: 6374

Bravo AF: 0.444

Asia WGS AF: 0.715 AC: 2483 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	4.4
DANN	Benign	0.88
PhyloP100		-1.2
Mutation Taster		=100/0	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: rs27498; hg19: chr3-10334021;