rs482204

Variant names:

• chr3-172445039-G-A
• rs482204
• NM_198407.2:c.*122C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-172445039-G-A
• chr3-172445039-G-C
• chr3-172445039-G-T

Variant summary

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

The NM_198407.2(GHSR):​c.*122C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,091,134 control chromosomes in the GnomAD database, including 281,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (35419 hom., cov: 31)
  • Exomes 𝑓: 0.72 (245760 hom.)
• Consequence: GHSR NM_198407.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.60
• Publications: 6 publications found

Genes affected

GHSR (HGNC:4267): (growth hormone secretagogue receptor) This gene encodes a member of the G-protein coupled receptor family. The encoded protein may play a role in energy homeostasis and regulation of body weight. Two identified transcript variants are expressed in several tissues and are evolutionary conserved in fish and swine. One transcript, 1a, excises an intron and encodes the functional protein; this protein is the receptor for the Ghrelin ligand and defines a neuroendocrine pathway for growth hormone release. The second transcript (1b) retains the intron and does not function as a receptor for Ghrelin; however, it may function to attenuate activity of isoform 1a. Mutations in this gene are associated with autosomal idiopathic short stature.[provided by RefSeq, Apr 2010]

GHSR Gene-Disease associations (from GenCC):

• short stature due to GHSR deficiency

  Inheritance: AD, SD, AR Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-172445039-G-A is Benign according to our data. Variant chr3-172445039-G-A is described in ClinVar as Benign. ClinVar VariationId is 344196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHSR	NM_198407.2	c.*122C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000241256.3	NP_940799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHSR	ENST00000241256.3	c.*122C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_198407.2	ENSP00000241256.2

Frequencies

GnomAD3 genomes AF: 0.679 AC: 102909 AN: 151570 Hom.: 35407 Cov.: 31

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.704

GnomAD4 exome AF: 0.720 AC: 676064 AN: 939446 Hom.: 245760 AF XY: 0.712 AC XY: 345791 AN XY: 485810

African (AFR) AF: 0.584 AC: 13359 AN: 22856

American (AMR) AF: 0.756 AC: 31077 AN: 41124

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 15045 AN: 21628

East Asian (EAS) AF: 0.661 AC: 24520 AN: 37082

South Asian (SAS) AF: 0.517 AC: 37140 AN: 71796

European-Finnish (FIN) AF: 0.698 AC: 29838 AN: 42762

Middle Eastern (MID) AF: 0.726 AC: 3114 AN: 4292

European-Non Finnish (NFE) AF: 0.751 AC: 491399 AN: 654760

Other (OTH) AF: 0.709 AC: 30572 AN: 43146

GnomAD4 genome AF: 0.679 AC: 102972 AN: 151688 Hom.: 35419 Cov.: 31 AF XY: 0.674 AC XY: 50005 AN XY: 74146

African (AFR) AF: 0.576 AC: 23768 AN: 41268

American (AMR) AF: 0.716 AC: 10927 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2366 AN: 3464

East Asian (EAS) AF: 0.640 AC: 3310 AN: 5172

South Asian (SAS) AF: 0.499 AC: 2408 AN: 4822

European-Finnish (FIN) AF: 0.697 AC: 7337 AN: 10522

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50531 AN: 67876

Other (OTH) AF: 0.705 AC: 1487 AN: 2108

Alfa AF: 0.663 Hom.: 5396

Bravo AF: 0.683

Asia WGS AF: 0.557 AC: 1941 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Short stature due to growth hormone secretagogue receptor deficiency Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.011
DANN	Benign	0.33
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs482204; hg19: chr3-172162829;