Genetic Variant GHRLOS:n.596G>A (chr3-10292337-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.21

Publications

11 publications found

Variant links:

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]

GHRLOS links:

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]

GHRL links:

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ACMG classification

Classification was made for transcript

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 link	c.-766+505C>T		intron_variant	Intron 1 of 5	ENST00000335542.13	NP_057446.1	Q9UBU3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRL	ENST00000335542.13 link	c.-766+505C>T		intron_variant	Intron 1 of 5	1	NM_016362.5	ENSP00000335074.8		Q9UBU3-1

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66535

AN:

151900

Hom.:

15791

Cov.:

show subpopulations

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.:

AF XY:

0.423

AC XY:

1361

AN XY:

3220

show subpopulations

African (AFR)

AF:

0.421

AC:

AN:

American (AMR)

AF:

0.583

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.429

AC:

AN:

140

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.551

AC:

527

AN:

956

European-Finnish (FIN)

AF:

0.384

AC:

AN:

250

Middle Eastern (MID)

AF:

0.375

AC:

AN:

European-Non Finnish (NFE)

AF:

0.367

AC:

1491

AN:

4066

Other (OTH)

AF:

0.432

AC:

184

AN:

426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

127

191

254

318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.438

AC:

66575

AN:

152018

Hom.:

15802

Cov.:

AF XY:

0.450

AC XY:

33453

AN XY:

74292

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1810

3620

5429

7239

9049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.88

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over