rs2072621

Positions:

• chrX-151177387-C-A
• chrX-151177387-C-G
• chrX-151177387-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GPR50	NM_004224.3	c.187+479C>A		intron_variant		ENST00000218316.4
GPR50-AS1	NR_135300.1	n.450G>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR50	ENST00000218316.4	c.187+479C>A		intron_variant		1	NM_004224.3	P1
GPR50-AS1	ENST00000454196.1	n.450G>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.362 AC: 40536 AN: 112050 Hom.: 5500 Cov.: 24 AF XY: 0.354 AC XY: 12142 AN XY: 34344

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.: 39 Cov.: 0 AF XY: 0.577 AC XY: 82 AN XY: 142

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.472

Gnomad4 OTH exome AF: 0.486

GnomAD4 genome AF: 0.362 AC: 40533 AN: 112094 Hom.: 5496 Cov.: 24 AF XY: 0.353 AC XY: 12156 AN XY: 34400

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.0936

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.337

Alfa AF: 0.386 Hom.: 19227

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
DANN	Benign	0.93

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

LitVar

Other links and lift over

dbSNP: rs2072621; hg19: chrX-150345859;