dbSNP rs561077: GPR50:p.Thr532Ala (chrX-151181177-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004224.3(GPR50):c.1594A>G(p.Thr532Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,206,901 control chromosomes in the GnomAD database, including 75,857 homozygotes. There are 166,171 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 8070 hom., 13638 hem., cov: 21)

Exomes 𝑓: 0.42 ( 67787 hom. 152533 hem. )

Consequence

GPR50
NM_004224.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.00

Publications

26 publications found

Variant links:

Genes affected

GPR50 (HGNC:4506): (G protein-coupled receptor 50) This gene product belongs to the G-protein coupled receptor 1 family. Even though this protein shares similarity with the melatonin receptors, it does not bind melatonin, however, it inhibits melatonin receptor 1A function through heterodimerization. Polymorphic variants of this gene have been associated with bipolar affective disorder in women. [provided by RefSeq, Jan 2010]

GPR50 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.339485E-5).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR50	NM_004224.3 link	c.1594A>G	p.Thr532Ala	missense_variant	Exon 2 of 2	ENST00000218316.4	NP_004215.2	Q13585
GPR50	XM_011531216.3 link	c.853A>G	p.Thr285Ala	missense_variant	Exon 2 of 2		XP_011529518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR50	ENST00000218316.4 link	c.1594A>G	p.Thr532Ala	missense_variant	Exon 2 of 2	1	NM_004224.3	ENSP00000218316.3		Q13585

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

48658

AN:

109013

Hom.:

8073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.507

Gnomad AMI

AF:

0.472

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.397

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.461

GnomAD2 exomes

AF:

0.430

AC:

78100

AN:

181776

AF XY:

0.417

show subpopulations

Gnomad AFR exome

AF:

0.509

Gnomad AMR exome

AF:

0.536

Gnomad ASJ exome

AF:

0.399

Gnomad EAS exome

AF:

0.256

Gnomad FIN exome

AF:

0.445

Gnomad NFE exome

AF:

0.423

Gnomad OTH exome

AF:

0.451

GnomAD4 exome

AF:

0.425

AC:

466240

AN:

1097831

Hom.:

67787

Cov.:

AF XY:

0.420

AC XY:

152533

AN XY:

363257

show subpopulations

African (AFR)

AF:

0.513

AC:

13539

AN:

26396

American (AMR)

AF:

0.532

AC:

18722

AN:

35184

Ashkenazi Jewish (ASJ)

AF:

0.386

AC:

7482

AN:

19382

East Asian (EAS)

AF:

0.251

AC:

7583

AN:

30200

South Asian (SAS)

AF:

0.369

AC:

19966

AN:

54140

European-Finnish (FIN)

AF:

0.441

AC:

17883

AN:

40514

Middle Eastern (MID)

AF:

0.400

AC:

1655

AN:

4135

European-Non Finnish (NFE)

AF:

0.427

AC:

359337

AN:

841799

Other (OTH)

AF:

0.436

AC:

20073

AN:

46081

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

11320

22640

33961

45281

56601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12046

24092

36138

48184

60230

<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:

0.446

AC:

48699

AN:

109070

Hom.:

8070

Cov.:

AF XY:

0.434

AC XY:

13638

AN XY:

31444

show subpopulations

African (AFR)

AF:

0.508

AC:

15149

AN:

29847

American (AMR)

AF:

0.512

AC:

5261

AN:

10271

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1019

AN:

2621

East Asian (EAS)

AF:

0.250

AC:

854

AN:

3422

South Asian (SAS)

AF:

0.338

AC:

836

AN:

2476

European-Finnish (FIN)

AF:

0.427

AC:

2376

AN:

5564

Middle Eastern (MID)

AF:

0.403

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.421

AC:

22121

AN:

52505

Other (OTH)

AF:

0.460

AC:

682

AN:

1483

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

963

1926

2888

3851

4814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.428

Hom.:

34316

Bravo

AF:

0.457

TwinsUK

AF:

0.410

AC:

1520

ALSPAC

AF:

0.427

AC:

1235

ESP6500AA

AF:

0.499

AC:

1892

ESP6500EA

AF:

0.416

AC:

2782

ExAC

AF:

0.421

AC:

51034

EpiCase

AF:

0.426

EpiControl

AF:

0.419

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0060

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.043

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.15

MetaRNN

Benign

0.000053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.42

PhyloP100

-2.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.33

REVEL

Benign

0.076

Sift

Benign

0.55

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.058

MPC

0.14

ClinPred

0.0091

GERP RS

-3.2

Varity_R

0.027

gMVP

0.096

Mutation Taster

=98/2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over