3-172447373-A-G

Variant names:

• chr3-172447373-A-G
• rs2948694
• NM_198407.2:c.796+245T>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.796+245T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 350,730 control chromosomes in the GnomAD database, including 3,112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1751 hom., cov: 32)
  • Exomes 𝑓: 0.11 (1361 hom.)
• Consequence: GHSR NM_198407.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.788
• Publications: 21 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=-0.9).
• BP6: Variant 3-172447373-A-G is Benign according to our data. Variant chr3-172447373-A-G is described in ClinVar as Benign. ClinVar VariationId is 1286049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 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.796+245T>C		intron	N/A	NP_940799.1	Q92847-1
	GHSR	NM_004122.2		c.*171T>C		downstream_gene	N/A	NP_004113.1	Q92847-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHSR	ENST00000241256.3	TSL:1 MANE Select	c.796+245T>C		intron	N/A	ENSP00000241256.2	Q92847-1
	GHSR	ENST00000427970.1	TSL:6	c.*171T>C		downstream_gene	N/A	ENSP00000395344.1	Q92847-2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 20138 AN: 132780 Hom.: 1750 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.0664

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.107 AC: 23385 AN: 217818 Hom.: 1361 AF XY: 0.108 AC XY: 11208 AN XY: 103612

African (AFR) AF: 0.0836 AC: 322 AN: 3852

American (AMR) AF: 0.137 AC: 32 AN: 234

Ashkenazi Jewish (ASJ) AF: 0.0750 AC: 103 AN: 1374

East Asian (EAS) AF: 0.360 AC: 306 AN: 850

South Asian (SAS) AF: 0.317 AC: 1344 AN: 4246

European-Finnish (FIN) AF: 0.224 AC: 13 AN: 58

Middle Eastern (MID) AF: 0.0708 AC: 30 AN: 424

European-Non Finnish (NFE) AF: 0.102 AC: 20334 AN: 199546

Other (OTH) AF: 0.125 AC: 901 AN: 7234

GnomAD4 genome AF: 0.152 AC: 20150 AN: 132912 Hom.: 1751 Cov.: 32 AF XY: 0.164 AC XY: 10569 AN XY: 64272

African (AFR) AF: 0.118 AC: 4315 AN: 36674

American (AMR) AF: 0.180 AC: 2173 AN: 12078

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 258 AN: 3190

East Asian (EAS) AF: 0.403 AC: 1831 AN: 4548

South Asian (SAS) AF: 0.390 AC: 1689 AN: 4330

European-Finnish (FIN) AF: 0.278 AC: 2385 AN: 8584

Middle Eastern (MID) AF: 0.0593 AC: 16 AN: 270

European-Non Finnish (NFE) AF: 0.116 AC: 7027 AN: 60640

Other (OTH) AF: 0.137 AC: 243 AN: 1772

Alfa AF: 0.117 Hom.: 2090

Bravo AF: 0.119

Asia WGS AF: 0.353 AC: 1222 AN: 3478

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.057
DANN	Benign	0.42
PhyloP100		-0.79
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: rs2948694; hg19: chr3-172165163;