3-172448354-G-A

Variant names:

• chr3-172448354-G-A
• rs2232165
• NM_198407.2:c.60C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_198407.2(GHSR):​c.60C>T​(p.Asp20Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0294 in 1,601,884 control chromosomes in the GnomAD database, including 984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (192 hom., cov: 32)
  • Exomes 𝑓: 0.028 (792 hom.)
• Consequence: GHSR NM_198407.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0300
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-172448354-G-A is Benign according to our data. Variant chr3-172448354-G-A is described in ClinVar as Benign. ClinVar VariationId is 344202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHSR	NM_198407.2	c.60C>T	p.Asp20Asp	synonymous_variant	Exon 1 of 2	ENST00000241256.3	NP_940799.1
GHSR	NM_004122.2	c.60C>T	p.Asp20Asp	synonymous_variant	Exon 1 of 1		NP_004113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHSR	ENST00000241256.3	c.60C>T	p.Asp20Asp	synonymous_variant	Exon 1 of 2	1	NM_198407.2	ENSP00000241256.2
GHSR	ENST00000427970.1	c.60C>T	p.Asp20Asp	synonymous_variant	Exon 1 of 1	6		ENSP00000395344.1

Frequencies

GnomAD3 genomes AF: 0.0386 AC: 5883 AN: 152216 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.0764

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0237

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0412

Gnomad FIN AF: 0.00847

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0274

Gnomad OTH AF: 0.0411

GnomAD2 exomes AF: 0.0291 AC: 6886 AN: 236764 AF XY: 0.0296

Gnomad AFR exome AF: 0.0769

Gnomad AMR exome AF: 0.0142

Gnomad ASJ exome AF: 0.0321

Gnomad EAS exome AF: 0.000277

Gnomad FIN exome AF: 0.0103

Gnomad NFE exome AF: 0.0283

Gnomad OTH exome AF: 0.0339

GnomAD4 exome AF: 0.0284 AC: 41225 AN: 1449550 Hom.: 792 Cov.: 37 AF XY: 0.0289 AC XY: 20843 AN XY: 721482

African (AFR) AF: 0.0821 AC: 2748 AN: 33468

American (AMR) AF: 0.0157 AC: 703 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.0326 AC: 851 AN: 26096

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39688

South Asian (SAS) AF: 0.0486 AC: 4187 AN: 86226

European-Finnish (FIN) AF: 0.00979 AC: 408 AN: 41664

Middle Eastern (MID) AF: 0.0686 AC: 392 AN: 5718

European-Non Finnish (NFE) AF: 0.0270 AC: 29963 AN: 1111726

Other (OTH) AF: 0.0326 AC: 1963 AN: 60296

GnomAD4 genome AF: 0.0387 AC: 5894 AN: 152334 Hom.: 192 Cov.: 32 AF XY: 0.0380 AC XY: 2830 AN XY: 74492

African (AFR) AF: 0.0765 AC: 3182 AN: 41584

American (AMR) AF: 0.0236 AC: 361 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4828

European-Finnish (FIN) AF: 0.00847 AC: 90 AN: 10624

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0274 AC: 1863 AN: 68028

Other (OTH) AF: 0.0406 AC: 86 AN: 2116

Alfa AF: 0.0302 Hom.: 137

Bravo AF: 0.0411

Asia WGS AF: 0.0230 AC: 80 AN: 3478

EpiCase AF: 0.0278

EpiControl AF: 0.0285

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.89
CADD	Benign	2.5
DANN	Benign	0.46
PhyloP100		0.030
PromoterAI		0.0064	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: rs2232165; hg19: chr3-172166144;