dbSNP rs495225: GHSR:p.Gly57Gly (chr3-172448243-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_198407.2(GHSR):c.171C>T(p.Gly57Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 1,613,588 control chromosomes in the GnomAD database, including 384,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31186 hom., cov: 33)

Exomes 𝑓: 0.69 ( 353194 hom. )

Consequence

GHSR
NM_198407.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.642

Publications

36 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 -16 ACMG points.

BP6

Variant 3-172448243-G-A is Benign according to our data. Variant chr3-172448243-G-A is described in ClinVar as Benign. ClinVar VariationId is 263109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 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.171C>T	p.Gly57Gly	synonymous	Exon 1 of 2	NP_940799.1	Q92847-1
	GHSR	NM_004122.2		c.171C>T	p.Gly57Gly	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.171C>T	p.Gly57Gly	synonymous	Exon 1 of 2	ENSP00000241256.2	Q92847-1
	GHSR	ENST00000427970.1	TSL:6	c.171C>T	p.Gly57Gly	synonymous	Exon 1 of 1	ENSP00000395344.1	Q92847-2

Frequencies

GnomAD3 genomes

AF:

0.630

AC:

95803

AN:

152044

Hom.:

31184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.465

Gnomad AMI

AF:

0.689

Gnomad AMR

AF:

0.689

Gnomad ASJ

AF:

0.659

Gnomad EAS

AF:

0.639

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.688

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.717

Gnomad OTH

AF:

0.656

GnomAD2 exomes

AF:

0.662

AC:

164382

AN:

248238

AF XY:

0.655

show subpopulations

Gnomad AFR exome

AF:

0.464

Gnomad AMR exome

AF:

0.753

Gnomad ASJ exome

AF:

0.663

Gnomad EAS exome

AF:

0.642

Gnomad FIN exome

AF:

0.683

Gnomad NFE exome

AF:

0.719

Gnomad OTH exome

AF:

0.665

GnomAD4 exome

AF:

0.691

AC:

1009895

AN:

1461426

Hom.:

353194

Cov.:

AF XY:

0.685

AC XY:

498089

AN XY:

726986

show subpopulations

African (AFR)

AF:

0.455

AC:

15233

AN:

33480

American (AMR)

AF:

0.739

AC:

33022

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.663

AC:

17335

AN:

26134

East Asian (EAS)

AF:

0.658

AC:

26138

AN:

39694

South Asian (SAS)

AF:

0.462

AC:

39876

AN:

86250

European-Finnish (FIN)

AF:

0.687

AC:

36464

AN:

53048

Middle Eastern (MID)

AF:

0.649

AC:

3740

AN:

5766

European-Non Finnish (NFE)

AF:

0.717

AC:

797613

AN:

1111958

Other (OTH)

AF:

0.670

AC:

40474

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

20397

40794

61192

81589

101986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19782

39564

59346

79128

98910

<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:

0.630

AC:

95837

AN:

152162

Hom.:

31186

Cov.:

AF XY:

0.627

AC XY:

46615

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.464

AC:

19271

AN:

41516

American (AMR)

AF:

0.689

AC:

10542

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.659

AC:

2286

AN:

3470

East Asian (EAS)

AF:

0.639

AC:

3295

AN:

5160

South Asian (SAS)

AF:

0.458

AC:

2209

AN:

4824

European-Finnish (FIN)

AF:

0.688

AC:

7285

AN:

10592

Middle Eastern (MID)

AF:

0.680

AC:

200

AN:

294

European-Non Finnish (NFE)

AF:

0.717

AC:

48731

AN:

67982

Other (OTH)

AF:

0.658

AC:

1390

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1757

3513

5270

7026

8783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<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:

0.687

Hom.:

55605

Bravo

AF:

0.630

Asia WGS

AF:

0.526

AC:

1836

AN:

3478

EpiCase

AF:

0.701

EpiControl

AF:

0.716

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.64

PromoterAI

0.00020

Neutral

(source)

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.29

Position offset: 6

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