rs35682

Variant names:

• chr3-10287098-G-A
• rs35682
• ENST00000475759.5:n.275C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-10287098-G-A
• chr3-10287098-G-C

Variant summary

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

The ENST00000475759.5(GHRL):​n.275C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 241,126 control chromosomes in the GnomAD database, including 42,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26885 hom., cov: 32)
  • Exomes 𝑓: 0.58 (15579 hom.)
• Consequence: GHRL ENST00000475759.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.497
• Publications: 30 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=-0.9).
• BP6: Variant 3-10287098-G-A is Benign according to our data. Variant chr3-10287098-G-A is described in ClinVar as Benign. ClinVar VariationId is 1174428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHRL	NM_016362.5	c.226-286C>T		intron_variant	Intron 4 of 5	ENST00000335542.13	NP_057446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHRL	ENST00000335542.13	c.226-286C>T		intron_variant	Intron 4 of 5	1	NM_016362.5	ENSP00000335074.8

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89053 AN: 151980 Hom.: 26864 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.569

GnomAD4 exome AF: 0.578 AC: 51477 AN: 89028 Hom.: 15579 Cov.: 0 AF XY: 0.591 AC XY: 27730 AN XY: 46948

African (AFR) AF: 0.595 AC: 1692 AN: 2842

American (AMR) AF: 0.651 AC: 2164 AN: 3326

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1608 AN: 2812

East Asian (EAS) AF: 0.984 AC: 4740 AN: 4818

South Asian (SAS) AF: 0.791 AC: 7269 AN: 9186

European-Finnish (FIN) AF: 0.555 AC: 3435 AN: 6186

Middle Eastern (MID) AF: 0.581 AC: 243 AN: 418

European-Non Finnish (NFE) AF: 0.506 AC: 27342 AN: 54046

Other (OTH) AF: 0.553 AC: 2984 AN: 5394

GnomAD4 genome AF: 0.586 AC: 89125 AN: 152098 Hom.: 26885 Cov.: 32 AF XY: 0.597 AC XY: 44403 AN XY: 74368

African (AFR) AF: 0.615 AC: 25518 AN: 41482

American (AMR) AF: 0.656 AC: 10036 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2025 AN: 3470

East Asian (EAS) AF: 0.976 AC: 5042 AN: 5168

South Asian (SAS) AF: 0.818 AC: 3956 AN: 4834

European-Finnish (FIN) AF: 0.554 AC: 5862 AN: 10578

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34771 AN: 67952

Other (OTH) AF: 0.569 AC: 1202 AN: 2114

Alfa AF: 0.540 Hom.: 54879

Bravo AF: 0.591

Asia WGS AF: 0.850 AC: 2956 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.67
PhyloP100		-0.50
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: rs35682; hg19: chr3-10328782;