dbSNP rs2072621: GPR50:c.187+479C>A (chrX-151177387-C-A) – 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.187+479C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 112,686 control chromosomes in the GnomAD database, including 5,535 homozygotes. There are 12,238 hemizygotes in GnomAD. 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 0.36 ( 5496 hom., 12156 hem., cov: 24)

Exomes 𝑓: 0.45 ( 39 hom. 82 hem. )

Consequence

GPR50
NM_004224.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0270

Publications

8 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:

GPR50-AS1 (HGNC:40259): (GPR50 antisense RNA 1)

GPR50-AS1 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 (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR50	NM_004224.3 link	c.187+479C>A		intron_variant	Intron 1 of 1	ENST00000218316.4	NP_004215.2	Q13585
GPR50-AS1	NR_135300.1 link	n.450G>T		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPR50	ENST00000218316.4 link	c.187+479C>A	intron_variant	Intron 1 of 1	1	NM_004224.3	ENSP00000218316.3	Q13585
GPR50-AS1	ENST00000454196.1 link	n.450G>T	non_coding_transcript_exon_variant	Exon 1 of 3	2
GPR50-AS1	ENST00000835194.1 link	n.430G>T	non_coding_transcript_exon_variant	Exon 1 of 2
GPR50-AS1	ENST00000835195.1 link	n.419G>T	non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

40536

AN:

112050

Hom.:

5500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.0935

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.245

Gnomad NFE

AF:

0.430

Gnomad OTH

AF:

0.341

GnomAD4 exome

AF:

0.448

AC:

265

AN:

592

Hom.:

Cov.:

AF XY:

0.577

AC XY:

AN XY:

142

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

AN:

East Asian (EAS)

AF:

0.182

AC:

AN:

South Asian (SAS)

AF:

0.313

AC:

AN:

European-Finnish (FIN)

AF:

0.409

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.472

AC:

216

AN:

458

Other (OTH)

AF:

0.486

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.362

AC:

40533

AN:

112094

Hom.:

5496

Cov.:

AF XY:

0.353

AC XY:

12156

AN XY:

34400

show subpopulations

African (AFR)

AF:

0.317

AC:

9804

AN:

30974

American (AMR)

AF:

0.283

AC:

3073

AN:

10843

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

647

AN:

2642

East Asian (EAS)

AF:

0.0936

AC:

328

AN:

3505

South Asian (SAS)

AF:

0.242

AC:

678

AN:

2802

European-Finnish (FIN)

AF:

0.398

AC:

2429

AN:

6105

Middle Eastern (MID)

AF:

0.246

AC:

AN:

211

European-Non Finnish (NFE)

AF:

0.430

AC:

22710

AN:

52817

Other (OTH)

AF:

0.337

AC:

515

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

940

1880

2821

3761

4701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.389

Hom.:

23108

Bravo

AF:

0.346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.2

(source)

DANN

Benign

0.93

PhyloP100

0.027

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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