Genetic Variant NM_004224.3:c.188-15C>T (chrX-151179756-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004224.3(GPR50):c.188-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.86 ( 29006 hom., 27133 hem., cov: 22)

Exomes 𝑓: 0.87 ( 269006 hom. 269802 hem. )

Failed GnomAD Quality Control

Consequence

GPR50
NM_004224.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

12 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR50	NM_004224.3 link	c.188-15C>T		intron_variant	Intron 1 of 1	ENST00000218316.4	NP_004215.2	Q13585
GPR50	XM_011531216.3 link	c.-336C>T		upstream_gene_variant			XP_011529518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR50	ENST00000218316.4 link	c.188-15C>T		intron_variant	Intron 1 of 1	1	NM_004224.3	ENSP00000218316.3		Q13585

Frequencies

GnomAD3 genomes

AF:

0.859

AC:

94079

AN:

109573

Hom.:

29009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.891

Gnomad AMI

AF:

0.924

Gnomad AMR

AF:

0.692

Gnomad ASJ

AF:

0.868

Gnomad EAS

AF:

0.728

Gnomad SAS

AF:

0.871

Gnomad FIN

AF:

0.883

Gnomad MID

AF:

0.880

Gnomad NFE

AF:

0.878

Gnomad OTH

AF:

0.824

GnomAD2 exomes

AF:

0.829

AC:

118804

AN:

143339

AF XY:

0.841

show subpopulations

Gnomad AFR exome

AF:

0.896

Gnomad AMR exome

AF:

0.625

Gnomad ASJ exome

AF:

0.891

Gnomad EAS exome

AF:

0.722

Gnomad FIN exome

AF:

0.886

Gnomad NFE exome

AF:

0.881

Gnomad OTH exome

AF:

0.821

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.874

AC:

883325

AN:

1010817

Hom.:

269006

Cov.:

AF XY:

0.877

AC XY:

269802

AN XY:

307525

show subpopulations

African (AFR)

AF:

0.899

AC:

21693

AN:

24120

American (AMR)

AF:

0.631

AC:

18277

AN:

28962

Ashkenazi Jewish (ASJ)

AF:

0.889

AC:

14184

AN:

15960

East Asian (EAS)

AF:

0.687

AC:

20322

AN:

29566

South Asian (SAS)

AF:

0.874

AC:

39690

AN:

45405

European-Finnish (FIN)

AF:

0.883

AC:

33942

AN:

38437

Middle Eastern (MID)

AF:

0.856

AC:

3258

AN:

3807

European-Non Finnish (NFE)

AF:

0.889

AC:

695433

AN:

781902

Other (OTH)

AF:

0.856

AC:

36526

AN:

42658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3937

7873

11810

15746

19683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.859

AC:

94117

AN:

109625

Hom.:

29006

Cov.:

AF XY:

0.851

AC XY:

27133

AN XY:

31865

show subpopulations

African (AFR)

AF:

0.890

AC:

26751

AN:

30046

American (AMR)

AF:

0.691

AC:

7151

AN:

10342

Ashkenazi Jewish (ASJ)

AF:

0.868

AC:

2281

AN:

2629

East Asian (EAS)

AF:

0.729

AC:

2540

AN:

3486

South Asian (SAS)

AF:

0.871

AC:

2080

AN:

2388

European-Finnish (FIN)

AF:

0.883

AC:

5072

AN:

5744

Middle Eastern (MID)

AF:

0.883

AC:

189

AN:

214

European-Non Finnish (NFE)

AF:

0.878

AC:

46198

AN:

52605

Other (OTH)

AF:

0.823

AC:

1227

AN:

1491

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

479

958

1437

1916

2395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.872

Hom.:

17422

Bravo

AF:

0.846

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.88

(source)

DANN

Benign

0.74

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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NM_004224.3:c.188-15C>T

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