rs13440581

Variant names:

• chrX-151181399-A-G
• rs13440581
• NM_004224.3:c.1816A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004224.3(GPR50):​c.1816A>G​(p.Ile606Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 110,801 control chromosomes in the GnomAD database, including 9,053 homozygotes. There are 14,558 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 (9053 hom., 14558 hem., cov: 23)
  • Exomes 𝑓: 0.55 (115734 hom. 190785 hem.)
  • Failed GnomAD Quality Control
• Consequence: GPR50 NM_004224.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 21 publications found

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]

ENSG00000269993 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=2.012317E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR50	NM_004224.3	c.1816A>G	p.Ile606Val	missense_variant	Exon 2 of 2	ENST00000218316.4	NP_004215.2
GPR50	XM_011531216.3	c.1075A>G	p.Ile359Val	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	c.1816A>G	p.Ile606Val	missense_variant	Exon 2 of 2	1	NM_004224.3	ENSP00000218316.3
ENSG00000269993	ENST00000602313.2	n.-213A>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.450 AC: 49878 AN: 110747 Hom.: 9057 Cov.: 23

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.457

GnomAD2 exomes AF: 0.449 AC: 75716 AN: 168779 AF XY: 0.465

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.289

Gnomad ASJ exome AF: 0.590

Gnomad EAS exome AF: 0.0101

Gnomad FIN exome AF: 0.608

Gnomad NFE exome AF: 0.587

Gnomad OTH exome AF: 0.489

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.547 AC: 590474 AN: 1080144 Hom.: 115734 Cov.: 30 AF XY: 0.545 AC XY: 190785 AN XY: 350376

African (AFR) AF: 0.273 AC: 7133 AN: 26161

American (AMR) AF: 0.295 AC: 10150 AN: 34373

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 11458 AN: 18956

East Asian (EAS) AF: 0.00697 AC: 209 AN: 29989

South Asian (SAS) AF: 0.368 AC: 19430 AN: 52729

European-Finnish (FIN) AF: 0.604 AC: 21788 AN: 36093

Middle Eastern (MID) AF: 0.529 AC: 2158 AN: 4076

European-Non Finnish (NFE) AF: 0.595 AC: 495057 AN: 832278

Other (OTH) AF: 0.508 AC: 23091 AN: 45489

GnomAD4 genome AF: 0.450 AC: 49879 AN: 110801 Hom.: 9053 Cov.: 23 AF XY: 0.440 AC XY: 14558 AN XY: 33057

African (AFR) AF: 0.274 AC: 8379 AN: 30536

American (AMR) AF: 0.358 AC: 3761 AN: 10513

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 1598 AN: 2628

East Asian (EAS) AF: 0.0138 AC: 49 AN: 3555

South Asian (SAS) AF: 0.313 AC: 806 AN: 2576

European-Finnish (FIN) AF: 0.590 AC: 3437 AN: 5823

Middle Eastern (MID) AF: 0.509 AC: 108 AN: 212

European-Non Finnish (NFE) AF: 0.582 AC: 30732 AN: 52792

Other (OTH) AF: 0.452 AC: 676 AN: 1497

Alfa AF: 0.523 Hom.: 39809

Bravo AF: 0.421

TwinsUK AF: 0.605 AC: 2244

ALSPAC AF: 0.595 AC: 1718

ESP6500AA AF: 0.271 AC: 996

ESP6500EA AF: 0.583 AC: 3870

ExAC AF: 0.455 AC: 55079

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.11
DANN	Benign	0.60
DEOGEN2	Benign	0.058	T
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.000020	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.97	L
PhyloP100		-1.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.069
Sift	Benign	0.22	T
Sift4G	Uncertain	0.022	D
Polyphen		0.010	B
Vest4		0.062
MPC		0.12
ClinPred		0.011	T
GERP RS		2.1
Varity_R		0.058
gMVP		0.055
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13440581; hg19: chrX-150349871; COSMIC: COSV54438870; COSMIC: COSV54438870;