3-10288693-C-T

Variant names:

• chr3-10288693-C-T
• rs42451
• NM_016362.5:c.225+1069G>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.225+1069G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,156 control chromosomes in the GnomAD database, including 4,580 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 0.24 (4580 hom., cov: 32)
• Consequence: GHRL NM_016362.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRL	NM_016362.5	MANE Select	c.225+1069G>A		intron	N/A	NP_057446.1	Q9UBU3-1
	GHRL	NM_001302821.2		c.225+1069G>A		intron	N/A	NP_001289750.1	Q9UBU3-1
	GHRL	NM_001302822.2		c.225+1069G>A		intron	N/A	NP_001289751.1	Q9UBU3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRL	ENST00000335542.13	TSL:1 MANE Select	c.225+1069G>A		intron	N/A	ENSP00000335074.8	Q9UBU3-1
	GHRL	ENST00000429122.1	TSL:1	c.225+1069G>A		intron	N/A	ENSP00000414819.1	Q9UBU3-1
	GHRL	ENST00000457360.5	TSL:1	c.225+1069G>A		intron	N/A	ENSP00000391406.1	Q9UBU3-1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36903 AN: 152038 Hom.: 4576 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.243 AC: 36920 AN: 152156 Hom.: 4580 Cov.: 32 AF XY: 0.240 AC XY: 17823 AN XY: 74372

African (AFR) AF: 0.221 AC: 9191 AN: 41512

American (AMR) AF: 0.202 AC: 3097 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3468

East Asian (EAS) AF: 0.126 AC: 651 AN: 5182

South Asian (SAS) AF: 0.222 AC: 1068 AN: 4812

European-Finnish (FIN) AF: 0.203 AC: 2149 AN: 10576

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18668 AN: 67998

Other (OTH) AF: 0.258 AC: 544 AN: 2112

Alfa AF: 0.253 Hom.: 6470

Bravo AF: 0.240

Asia WGS AF: 0.186 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.69
DANN	Benign	0.61
PhyloP100		-2.5
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: rs42451; hg19: chr3-10330377;