rs26312

Variant names:

• chr3-10291174-G-A
• rs26312
• NM_016362.5:c.-488C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-10291174-G-A
• chr3-10291174-G-C

Variant summary

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

The NM_016362.5(GHRL):​c.-488C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 985,506 control chromosomes in the GnomAD database, including 9,391 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 0.16 (2344 hom., cov: 33)
  • Exomes 𝑓: 0.13 (7047 hom.)
• Consequence: GHRL NM_016362.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 17 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 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.-488C>T		5_prime_UTR	Exon 2 of 6	NP_057446.1	Q9UBU3-1
	GHRL	NM_001134941.3		c.-488C>T		5_prime_UTR	Exon 2 of 6	NP_001128413.1	Q9UBU3-2
	GHRL	NM_001302821.2		c.-305+66C>T		intron	N/A	NP_001289750.1	Q9UBU3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHRL	ENST00000335542.13	TSL:1 MANE Select	c.-488C>T		5_prime_UTR	Exon 2 of 6	ENSP00000335074.8	Q9UBU3-1
	GHRL	ENST00000287656.11	TSL:1	c.-488C>T		5_prime_UTR	Exon 2 of 6	ENSP00000287656.7	Q9UBU3-2
	GHRL	ENST00000429122.1	TSL:1	c.-226-262C>T		intron	N/A	ENSP00000414819.1	Q9UBU3-1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24560 AN: 152126 Hom.: 2338 Cov.: 33

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.125 AC: 104551 AN: 833262 Hom.: 7047 Cov.: 32 AF XY: 0.125 AC XY: 48271 AN XY: 384844

African (AFR) AF: 0.216 AC: 3407 AN: 15796

American (AMR) AF: 0.110 AC: 108 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 795 AN: 5154

East Asian (EAS) AF: 0.421 AC: 1531 AN: 3640

South Asian (SAS) AF: 0.162 AC: 2665 AN: 16466

European-Finnish (FIN) AF: 0.113 AC: 32 AN: 284

Middle Eastern (MID) AF: 0.148 AC: 239 AN: 1620

European-Non Finnish (NFE) AF: 0.120 AC: 91733 AN: 762008

Other (OTH) AF: 0.148 AC: 4041 AN: 27310

GnomAD4 genome AF: 0.161 AC: 24586 AN: 152244 Hom.: 2344 Cov.: 33 AF XY: 0.163 AC XY: 12167 AN XY: 74440

African (AFR) AF: 0.214 AC: 8873 AN: 41522

American (AMR) AF: 0.126 AC: 1934 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 494 AN: 3470

East Asian (EAS) AF: 0.415 AC: 2146 AN: 5172

South Asian (SAS) AF: 0.173 AC: 834 AN: 4830

European-Finnish (FIN) AF: 0.152 AC: 1612 AN: 10606

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8316 AN: 68018

Other (OTH) AF: 0.146 AC: 308 AN: 2114

Alfa AF: 0.137 Hom.: 204

Bravo AF: 0.160

Asia WGS AF: 0.261 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.57
PhyloP100		-1.5
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: rs26312; hg19: chr3-10332858;