rs775520411

Variant names:

• chrX-151180052-G-A
• rs775520411
• NM_004224.3:c.469G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-151180052-G-A
• chrX-151180052-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004224.3(GPR50):​c.469G>A​(p.Val157Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,097,667 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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: not found (cov: 22)
  • Exomes 𝑓: 0.0000046 (0 hom. 2 hem.)
• Consequence: GPR50 NM_004224.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.037295997).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR50	NM_004224.3	c.469G>A	p.Val157Ile	missense_variant	Exon 2 of 2	ENST00000218316.4	NP_004215.2
GPR50	XM_011531216.3	c.-40G>A		5_prime_UTR_variant	Exon 1 of 2		XP_011529518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR50	ENST00000218316.4	c.469G>A	p.Val157Ile	missense_variant	Exon 2 of 2	1	NM_004224.3	ENSP00000218316.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.00000550 AC: 1 AN: 181821 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67363

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000456 AC: 5 AN: 1097667 Hom.: 0 Cov.: 33 AF XY: 0.00000551 AC XY: 2 AN XY: 363031

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000370

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000356

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0010
DANN	Benign	0.85
DEOGEN2	Benign	0.047	T
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.025
Sift	Benign	0.56	T
Sift4G	Benign	0.23	T
Polyphen		0.0010	B
Vest4		0.036
MutPred		0.59		Loss of catalytic residue at V157 (P = 0.2285);
MVP		0.23
MPC		0.12
ClinPred		0.049	T
GERP RS		-7.5
Varity_R		0.027
gMVP		0.24

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

Other links and lift over

dbSNP: rs775520411; hg19: chrX-150348524; COSMIC: COSV54442949; COSMIC: COSV54442949;