dbSNP rs572169: GHSR:p.Arg159Arg (chr3-172447937-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_198407.2(GHSR):c.477G>A(p.Arg159Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,612,494 control chromosomes in the GnomAD database, including 76,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5664 hom., cov: 32)

Exomes 𝑓: 0.30 ( 70455 hom. )

Consequence

GHSR
NM_198407.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.13

Publications

92 publications found

Variant links:

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

GHSR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 3-172447937-C-T is Benign according to our data. Variant chr3-172447937-C-T is described in ClinVar as Benign. ClinVar VariationId is 263110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 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.477G>A	p.Arg159Arg	synonymous	Exon 1 of 2	NP_940799.1	Q92847-1
	GHSR	NM_004122.2		c.477G>A	p.Arg159Arg	synonymous	Exon 1 of 1	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.477G>A	p.Arg159Arg	synonymous	Exon 1 of 2	ENSP00000241256.2	Q92847-1
	GHSR	ENST00000427970.1	TSL:6	c.477G>A	p.Arg159Arg	synonymous	Exon 1 of 1	ENSP00000395344.1	Q92847-2

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37830

AN:

151994

Hom.:

5655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0835

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.439

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.236

GnomAD2 exomes

AF:

0.308

AC:

77121

AN:

250532

AF XY:

0.302

show subpopulations

Gnomad AFR exome

AF:

0.0829

Gnomad AMR exome

AF:

0.422

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.461

Gnomad FIN exome

AF:

0.331

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.305

AC:

444746

AN:

1460384

Hom.:

70455

Cov.:

AF XY:

0.301

AC XY:

218818

AN XY:

726140

show subpopulations

African (AFR)

AF:

0.0733

AC:

2453

AN:

33460

American (AMR)

AF:

0.405

AC:

18076

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

5051

AN:

26126

East Asian (EAS)

AF:

0.432

AC:

17121

AN:

39660

South Asian (SAS)

AF:

0.229

AC:

19724

AN:

86242

European-Finnish (FIN)

AF:

0.332

AC:

17710

AN:

53376

Middle Eastern (MID)

AF:

0.171

AC:

985

AN:

5764

European-Non Finnish (NFE)

AF:

0.312

AC:

346520

AN:

1110754

Other (OTH)

AF:

0.284

AC:

17106

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

20730

41461

62191

82922

103652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11412

22824

34236

45648

57060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.249

AC:

37852

AN:

152110

Hom.:

5664

Cov.:

AF XY:

0.252

AC XY:

18772

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0835

AC:

3470

AN:

41548

American (AMR)

AF:

0.311

AC:

4751

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

678

AN:

3472

East Asian (EAS)

AF:

0.439

AC:

2256

AN:

5138

South Asian (SAS)

AF:

0.231

AC:

1111

AN:

4812

European-Finnish (FIN)

AF:

0.345

AC:

3648

AN:

10568

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.309

AC:

21018

AN:

67972

Other (OTH)

AF:

0.241

AC:

508

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1409

2817

4226

5634

7043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.289

Hom.:

31493

Bravo

AF:

0.245

Asia WGS

AF:

0.320

AC:

1115

AN:

3478

EpiCase

AF:

0.284

EpiControl

AF:

0.291

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Short stature due to growth hormone secretagogue receptor deficiency (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.5

(source)

DANN

Benign

0.73

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over