rs509035

Variant names:

• chr3-172445659-G-A
• rs509035
• NM_198407.2:c.797-194C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-172445659-G-A
• chr3-172445659-G-C
• chr3-172445659-G-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.797-194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,096 control chromosomes in the GnomAD database, including 5,693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5693 hom., cov: 32)
• Consequence: GHSR NM_198407.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0900
• Publications: 32 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=-0.81).
• BP6: Variant 3-172445659-G-A is Benign according to our data. Variant chr3-172445659-G-A is described in ClinVar as Benign. ClinVar VariationId is 1222463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GHSR	NM_198407.2	c.797-194C>T		intron_variant	Intron 1 of 1	ENST00000241256.3	NP_940799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GHSR	ENST00000241256.3	c.797-194C>T		intron_variant	Intron 1 of 1	1	NM_198407.2	ENSP00000241256.2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37933 AN: 151978 Hom.: 5684 Cov.: 32

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.250 AC: 37954 AN: 152096 Hom.: 5693 Cov.: 32 AF XY: 0.253 AC XY: 18804 AN XY: 74328

African (AFR) AF: 0.0836 AC: 3472 AN: 41522

American (AMR) AF: 0.311 AC: 4759 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3468

East Asian (EAS) AF: 0.440 AC: 2279 AN: 5176

South Asian (SAS) AF: 0.232 AC: 1118 AN: 4826

European-Finnish (FIN) AF: 0.345 AC: 3639 AN: 10544

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21092 AN: 67972

Other (OTH) AF: 0.242 AC: 510 AN: 2110

Alfa AF: 0.289 Hom.: 27118

Bravo AF: 0.246

Asia WGS AF: 0.319 AC: 1112 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

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	-0.81
CADD	Benign	1.7
DANN	Benign	0.50
PhyloP100		0.090
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: rs509035; hg19: chr3-172163449;