chr3-10289914-C-T

Variant names:

• chr3-10289914-C-T
• rs182039551
• NM_016362.5:c.109-36G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016362.5(GHRL):​c.109-36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,531,540 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (168 hom.)
• Consequence: GHRL NM_016362.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0830
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-10289914-C-T is Benign according to our data. Variant chr3-10289914-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0742 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.109-36G>A		intron	N/A	NP_057446.1	Q9UBU3-1
	GHRL	NM_001302821.2		c.109-36G>A		intron	N/A	NP_001289750.1	Q9UBU3-1
	GHRL	NM_001302822.2		c.109-36G>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.109-36G>A		intron	N/A	ENSP00000335074.8	Q9UBU3-1
	GHRL	ENST00000429122.1	TSL:1	c.109-36G>A		intron	N/A	ENSP00000414819.1	Q9UBU3-1
	GHRL	ENST00000457360.5	TSL:1	c.109-36G>A		intron	N/A	ENSP00000391406.1	Q9UBU3-1

Frequencies

GnomAD3 genomes AF: 0.00489 AC: 744 AN: 152120 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.000821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.0122 AC: 2856 AN: 234682 AF XY: 0.00893

Gnomad AFR exome AF: 0.000808

Gnomad AMR exome AF: 0.0827

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00407

Gnomad FIN exome AF: 0.0000491

Gnomad NFE exome AF: 0.0000937

Gnomad OTH exome AF: 0.00848

GnomAD4 exome AF: 0.00260 AC: 3586 AN: 1379300 Hom.: 168 Cov.: 22 AF XY: 0.00213 AC XY: 1464 AN XY: 688058

African (AFR) AF: 0.000536 AC: 17 AN: 31714

American (AMR) AF: 0.0763 AC: 3268 AN: 42812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24094

East Asian (EAS) AF: 0.00313 AC: 123 AN: 39260

South Asian (SAS) AF: 0.000110 AC: 9 AN: 82014

European-Finnish (FIN) AF: 0.0000762 AC: 4 AN: 52516

Middle Eastern (MID) AF: 0.000181 AC: 1 AN: 5522

European-Non Finnish (NFE) AF: 0.0000498 AC: 52 AN: 1043996

Other (OTH) AF: 0.00195 AC: 112 AN: 57372

GnomAD4 genome AF: 0.00494 AC: 752 AN: 152240 Hom.: 20 Cov.: 32 AF XY: 0.00556 AC XY: 414 AN XY: 74436

African (AFR) AF: 0.000819 AC: 34 AN: 41530

American (AMR) AF: 0.0445 AC: 681 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68012

Other (OTH) AF: 0.00758 AC: 16 AN: 2110

Alfa AF: 0.000343 Hom.: 0

Bravo AF: 0.00824

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.32
PhyloP100		-0.083
PromoterAI		0.0084	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs182039551; hg19: chr3-10331598;