rs696217

Variant names:

• chr3-10289773-G-C
• NM_016362.5:c.214C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-10289773-G-C
• chr3-10289773-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016362.5(GHRL):​c.214C>G​(p.Leu72Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GHRL NM_016362.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27436188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHRL	NM_016362.5	c.214C>G	p.Leu72Val	missense_variant	Exon 4 of 6	ENST00000335542.13	NP_057446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRL	ENST00000335542.13	c.214C>G	p.Leu72Val	missense_variant	Exon 4 of 6	1	NM_016362.5	ENSP00000335074.8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451160 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 722686

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;.;.;.;.;T;T
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.80	.;.;T;D;T;D;.;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.27	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.8	L;.;L;.;.;.;L;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.77	N;N;N;N;N;N;N;N
REVEL	Benign	0.061
Sift	Benign	0.16	T;T;D;T;T;T;T;T
Sift4G	Benign	0.36	T;T;D;D;D;T;T;T
Polyphen		1.0	D;D;.;D;D;D;D;D
Vest4		0.43
MutPred		0.32		Loss of sheet (P = 0.0228);.;Loss of sheet (P = 0.0228);.;.;.;Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);
MVP		0.53
MPC		0.032
ClinPred		0.76	D
GERP RS		3.4
Varity_R		0.095
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-10331457;