rs565105

Variant names:

• chr3-172444327-G-T
• rs565105
• NM_198407.2:c.*834C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-172444327-G-T
• chr3-172444327-G-A
• chr3-172444327-G-C

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.*834C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,010 control chromosomes in the GnomAD database, including 35,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (35541 hom., cov: 32)
• Consequence: GHSR NM_198407.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.62
• Publications: 8 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: AR, AD, SD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-172444327-G-T is Benign according to our data. Variant chr3-172444327-G-T is described in ClinVar as Benign. ClinVar VariationId is 344186.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 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.*834C>A		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.*834C>A		3_prime_UTR	Exon 2 of 2	ENSP00000241256.2	Q92847-1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103179 AN: 151892 Hom.: 35532 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.679 AC: 103239 AN: 152010 Hom.: 35541 Cov.: 32 AF XY: 0.675 AC XY: 50118 AN XY: 74284

African (AFR) AF: 0.577 AC: 23909 AN: 41454

American (AMR) AF: 0.717 AC: 10952 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2372 AN: 3470

East Asian (EAS) AF: 0.639 AC: 3306 AN: 5172

South Asian (SAS) AF: 0.498 AC: 2404 AN: 4824

European-Finnish (FIN) AF: 0.698 AC: 7359 AN: 10548

Middle Eastern (MID) AF: 0.723 AC: 211 AN: 292

European-Non Finnish (NFE) AF: 0.745 AC: 50606 AN: 67950

Other (OTH) AF: 0.705 AC: 1489 AN: 2112

Alfa AF: 0.723 Hom.: 145779

Bravo AF: 0.683

Asia WGS AF: 0.556 AC: 1935 AN: 3474

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	-0.88
CADD	Benign	1.0
DANN	Benign	0.24
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs565105; hg19: chr3-172162117;