3-10290681-T-G

Variant names:

• chr3-10290681-T-G
• rs26802
• NM_016362.5:c.-30+35A>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.-30+35A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 996,408 control chromosomes in the GnomAD database, including 51,182 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 0.31 (7655 hom., cov: 32)
  • Exomes 𝑓: 0.32 (43527 hom.)
• Consequence: GHRL NM_016362.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 63 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 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.-30+35A>C		intron	N/A	NP_057446.1	Q9UBU3-1
	GHRL	NM_001302821.2		c.-30+35A>C		intron	N/A	NP_001289750.1	Q9UBU3-1
	GHRL	NM_001302822.2		c.-30+35A>C		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.-30+35A>C		intron	N/A	ENSP00000335074.8	Q9UBU3-1
	GHRL	ENST00000429122.1	TSL:1	c.-30+35A>C		intron	N/A	ENSP00000414819.1	Q9UBU3-1
	GHRL	ENST00000457360.5	TSL:1	c.-30+35A>C		intron	N/A	ENSP00000391406.1	Q9UBU3-1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47551 AN: 151892 Hom.: 7654 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.0837

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.317 AC: 268092 AN: 844398 Hom.: 43527 Cov.: 15 AF XY: 0.318 AC XY: 124474 AN XY: 391928

African (AFR) AF: 0.336 AC: 5481 AN: 16294

American (AMR) AF: 0.247 AC: 634 AN: 2570

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1868 AN: 5846

East Asian (EAS) AF: 0.0837 AC: 478 AN: 5714

South Asian (SAS) AF: 0.396 AC: 6653 AN: 16820

European-Finnish (FIN) AF: 0.271 AC: 746 AN: 2748

Middle Eastern (MID) AF: 0.407 AC: 688 AN: 1692

European-Non Finnish (NFE) AF: 0.318 AC: 242864 AN: 764456

Other (OTH) AF: 0.307 AC: 8680 AN: 28258

GnomAD4 genome AF: 0.313 AC: 47563 AN: 152010 Hom.: 7655 Cov.: 32 AF XY: 0.311 AC XY: 23140 AN XY: 74306

African (AFR) AF: 0.331 AC: 13721 AN: 41414

American (AMR) AF: 0.298 AC: 4554 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1129 AN: 3470

East Asian (EAS) AF: 0.0837 AC: 433 AN: 5176

South Asian (SAS) AF: 0.384 AC: 1850 AN: 4822

European-Finnish (FIN) AF: 0.276 AC: 2920 AN: 10576

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.321 AC: 21790 AN: 67958

Other (OTH) AF: 0.310 AC: 653 AN: 2106

Alfa AF: 0.314 Hom.: 11106

Bravo AF: 0.312

Asia WGS AF: 0.242 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.082
DANN	Benign	0.65
PhyloP100		-1.6
PromoterAI		0.021	Neutral
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: rs26802; hg19: chr3-10332365;