Variant X-151180138-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004224.3(GPR50):c.555C>T(p.Asn185=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00581 in 1,206,370 control chromosomes in the GnomAD database, including 20 homozygotes. There are 2,455 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 0 hom., 129 hem., cov: 22)

Exomes 𝑓: 0.0060 ( 20 hom. 2326 hem. )

Consequence

GPR50
NM_004224.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.02

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant X-151180138-C-T is Benign according to our data. Variant chrX-151180138-C-T is described in ClinVar as [Benign]. Clinvar id is 789366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.02 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.006 (6565/1094741) while in subpopulation SAS AF= 0.0163 (883/54132). AF 95% confidence interval is 0.0154. There are 20 homozygotes in gnomad4_exome. There are 2326 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 129 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR50	NM_004224.3 linkuse as main transcript	c.555C>T	p.Asn185=	synonymous_variant	2/2	ENST00000218316.4
GPR50	XM_011531216.3 linkuse as main transcript	c.1+46C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR50	ENST00000218316.4 linkuse as main transcript	c.555C>T	p.Asn185=	synonymous_variant	2/2	1	NM_004224.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00398

AC:

444

AN:

111575

Hom.:

Cov.:

AF XY:

0.00382

AC XY:

129

AN XY:

33729

show subpopulations

Gnomad AFR

AF:

0.000587

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00303

Gnomad ASJ

AF:

0.0148

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.000998

Gnomad MID

AF:

0.0210

Gnomad NFE

AF:

0.00571

Gnomad OTH

AF:

0.00468

GnomAD3 exomes

AF:

0.00561

AC:

1005

AN:

179054

Hom.:

AF XY:

0.00657

AC XY:

432

AN XY:

65784

show subpopulations

Gnomad AFR exome

AF:

0.00104

Gnomad AMR exome

AF:

0.00219

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.0000738

Gnomad SAS exome

AF:

0.0154

Gnomad FIN exome

AF:

0.00106

Gnomad NFE exome

AF:

0.00615

Gnomad OTH exome

AF:

0.00743

GnomAD4 exome

AF:

0.00600

AC:

6565

AN:

1094741

Hom.:

Cov.:

AF XY:

0.00644

AC XY:

2326

AN XY:

361177

show subpopulations

Gnomad4 AFR exome

AF:

0.000834

Gnomad4 AMR exome

AF:

0.00241

Gnomad4 ASJ exome

AF:

0.0127

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0163

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00594

Gnomad4 OTH exome

AF:

0.00521

GnomAD4 genome

AF:

0.00397

AC:

443

AN:

111629

Hom.:

Cov.:

AF XY:

0.00382

AC XY:

129

AN XY:

33793

show subpopulations

Gnomad4 AFR

AF:

0.000586

Gnomad4 AMR

AF:

0.00303

Gnomad4 ASJ

AF:

0.0148

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0126

Gnomad4 FIN

AF:

0.000998

Gnomad4 NFE

AF:

0.00571

Gnomad4 OTH

AF:

0.00462

Alfa

AF:

0.00633

Hom.:

Bravo

AF:

0.00416

EpiCase

AF:

0.00763

EpiControl

AF:

0.00782

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.7

DANN

Benign

0.81

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over