rs562416

Variant names:

• chr3-172444052-C-A
• rs562416
• NM_198407.2:c.*1109G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-172444052-C-A
• chr3-172444052-C-G
• chr3-172444052-C-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198407.2(GHSR):​c.*1109G>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 0.81 in 152,106 control chromosomes in the GnomAD database, including 50,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.81 (50530 hom., cov: 32)
• Consequence: GHSR NM_198407.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.305
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-172444052-C-A is Benign according to our data. Variant chr3-172444052-C-A is described in ClinVar as Benign. ClinVar VariationId is 344182.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198407.2. 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
	GHSR	NM_198407.2	MANE Select	c.*1109G>T		3_prime_UTR	Exon 2 of 2	NP_940799.1	Q92847-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHSR	ENST00000241256.3	TSL:1 MANE Select	c.*1109G>T		3_prime_UTR	Exon 2 of 2	ENSP00000241256.2	Q92847-1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123132 AN: 151988 Hom.: 50505 Cov.: 32

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.816

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.810 AC: 123207 AN: 152106 Hom.: 50530 Cov.: 32 AF XY: 0.816 AC XY: 60637 AN XY: 74354

African (AFR) AF: 0.674 AC: 27932 AN: 41456

American (AMR) AF: 0.859 AC: 13141 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2644 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5160 AN: 5186

South Asian (SAS) AF: 0.849 AC: 4098 AN: 4828

European-Finnish (FIN) AF: 0.923 AC: 9773 AN: 10592

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57656 AN: 67960

Other (OTH) AF: 0.819 AC: 1731 AN: 2114

Alfa AF: 0.778 Hom.: 3083

Bravo AF: 0.800

Asia WGS AF: 0.909 AC: 3153 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Short stature due to growth hormone secretagogue receptor deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.85
DANN	Benign	0.54
PhyloP100		0.30

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs562416;

hg19: chr3-172161842;