dbSNP rs11586015: GPR3:p.Gly17Gly (chr1-27393849-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_005281.4(GPR3):c.51C>A(p.Gly17Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 1,579,590 control chromosomes in the GnomAD database, including 400 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.014 ( 23 hom., cov: 33)

Exomes 𝑓: 0.021 ( 377 hom. )

Consequence

GPR3
NM_005281.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0510

Publications

7 publications found

Variant links:

Genes affected

GPR3 (HGNC:4484): (G protein-coupled receptor 3) This gene is a member of the G protein-coupled receptor family and is found in the cell membrane. G protein-coupled receptors, characterized by a seven transmembrane domain motif, are involved in translating outside signals into G protein mediated intracellular effects. The encoded protein activates adenylate cyclase and modulates amyloid-beta production in a mouse model, suggesting that it may play a role in Alzheimer's disease. [provided by RefSeq, Oct 2012]

GPR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP7

Synonymous conserved (PhyloP=0.051 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.014 (2137/152310) while in subpopulation NFE AF = 0.0218 (1484/68012). AF 95% confidence interval is 0.0209. There are 23 homozygotes in GnomAd4. There are 978 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR3	NM_005281.4 link	c.51C>A	p.Gly17Gly	synonymous_variant	Exon 2 of 2	ENST00000374024.4	NP_005272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR3	ENST00000374024.4 link	c.51C>A	p.Gly17Gly	synonymous_variant	Exon 2 of 2	1	NM_005281.4	ENSP00000363136.3

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2136

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00425

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0179

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00602

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0218

Gnomad OTH

AF:

0.0186

GnomAD2 exomes

AF:

0.0141

AC:

3275

AN:

232144

AF XY:

0.0147

show subpopulations

Gnomad AFR exome

AF:

0.00417

Gnomad AMR exome

AF:

0.0143

Gnomad ASJ exome

AF:

0.0243

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00586

Gnomad NFE exome

AF:

0.0214

Gnomad OTH exome

AF:

0.0178

GnomAD4 exome

AF:

0.0205

AC:

29295

AN:

1427280

Hom.:

377

Cov.:

AF XY:

0.0198

AC XY:

13984

AN XY:

705452

show subpopulations

African (AFR)

AF:

0.00390

AC:

127

AN:

32586

American (AMR)

AF:

0.0144

AC:

594

AN:

41328

Ashkenazi Jewish (ASJ)

AF:

0.0234

AC:

569

AN:

24360

East Asian (EAS)

AF:

0.0000511

AC:

AN:

39154

South Asian (SAS)

AF:

0.00274

AC:

227

AN:

82722

European-Finnish (FIN)

AF:

0.00581

AC:

299

AN:

51464

Middle Eastern (MID)

AF:

0.00995

AC:

AN:

5630

European-Non Finnish (NFE)

AF:

0.0240

AC:

26156

AN:

1091310

Other (OTH)

AF:

0.0215

AC:

1265

AN:

58726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1616

3232

4848

6464

8080

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1016

2032

3048

4064

5080

<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:

0.0140

AC:

2137

AN:

152310

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

978

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00423

AC:

176

AN:

41566

American (AMR)

AF:

0.0179

AC:

274

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00290

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00602

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0218

AC:

1484

AN:

68012

Other (OTH)

AF:

0.0184

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

111

222

333

444

555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0191

Hom.:

108

Bravo

AF:

0.0145

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.0

(source)

DANN

Benign

0.83

PhyloP100

0.051

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over