3-172447387-GGAGA-GGA

Variant names:

• chr3-172447387-GGA-G
• rs10618418
• NM_198407.2:c.796+229_796+230delTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000241256.3(GHSR):​c.796+229_796+230delTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 409,038 control chromosomes in the GnomAD database, including 102,587 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (35264 hom., cov: 0)
  • Exomes 𝑓: 0.72 (67323 hom.)
• Consequence: GHSR ENST00000241256.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94
• Publications: 4 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 -10 ACMG points.

• BP6: Variant 3-172447387-GGA-G is Benign according to our data. Variant chr3-172447387-GGA-G is described in ClinVar as Benign. ClinVar VariationId is 1239231.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: ENST00000241256.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHSR	NM_198407.2	MANE Select	c.796+229_796+230delTC		intron	N/A	NP_940799.1
	GHSR	NM_004122.2		c.*155_*156delTC		downstream_gene	N/A	NP_004113.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHSR	ENST00000241256.3	TSL:1 MANE Select	c.796+229_796+230delTC		intron	N/A	ENSP00000241256.2
	GHSR	ENST00000427970.1	TSL:6	c.*155_*156delTC		downstream_gene	N/A	ENSP00000395344.1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102613 AN: 151470 Hom.: 35257 Cov.: 0

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.703

GnomAD4 exome AF: 0.717 AC: 184638 AN: 257452 Hom.: 67323 AF XY: 0.717 AC XY: 87528 AN XY: 122100

African (AFR) AF: 0.533 AC: 2472 AN: 4642

American (AMR) AF: 0.748 AC: 208 AN: 278

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 1061 AN: 1566

East Asian (EAS) AF: 0.601 AC: 677 AN: 1126

South Asian (SAS) AF: 0.485 AC: 2607 AN: 5372

European-Finnish (FIN) AF: 0.656 AC: 59 AN: 90

Middle Eastern (MID) AF: 0.671 AC: 329 AN: 490

European-Non Finnish (NFE) AF: 0.728 AC: 171242 AN: 235234

Other (OTH) AF: 0.691 AC: 5983 AN: 8654

GnomAD4 genome AF: 0.677 AC: 102670 AN: 151586 Hom.: 35264 Cov.: 0 AF XY: 0.673 AC XY: 49804 AN XY: 74014

African (AFR) AF: 0.570 AC: 23553 AN: 41288

American (AMR) AF: 0.716 AC: 10914 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2381 AN: 3466

East Asian (EAS) AF: 0.639 AC: 3287 AN: 5142

South Asian (SAS) AF: 0.499 AC: 2389 AN: 4786

European-Finnish (FIN) AF: 0.696 AC: 7315 AN: 10510

Middle Eastern (MID) AF: 0.716 AC: 209 AN: 292

European-Non Finnish (NFE) AF: 0.745 AC: 50514 AN: 67846

Other (OTH) AF: 0.704 AC: 1479 AN: 2100

Alfa AF: 0.614 Hom.: 1741

Bravo AF: 0.682

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.9
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: rs10618418; hg19: chr3-172165177;