rs734852

Positions:

• chr1-27394463-G-A

Variant summary

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

The NM_005281.4(GPR3):​c.665G>A​(p.Arg222His) variant causes a missense change. The variant allele was found at a frequency of 0.00289 in 1,613,992 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.015 (49 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (45 hom.)
• Consequence: GPR3 NM_005281.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87

Genes affected

GPR3 (HGNC:4484): (G protein-coupled receptor 3) This gene is a member of the G protein-coupled receptor family and is found in the cell membrane. G protein-coupled receptors, characterized by a seven transmembrane domain motif, are involved in translating outside signals into G protein mediated intracellular effects. The encoded protein activates adenylate cyclase and modulates amyloid-beta production in a mouse model, suggesting that it may play a role in Alzheimer's disease. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010298997).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR3	NM_005281.4	c.665G>A	p.Arg222His	missense_variant	2/2	ENST00000374024.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR3	ENST00000374024.4	c.665G>A	p.Arg222His	missense_variant	2/2	1	NM_005281.4	P1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2283 AN: 152122 Hom.: 49 Cov.: 33

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00408 AC: 1024 AN: 251244 Hom.: 20 AF XY: 0.00292 AC XY: 396 AN XY: 135802

Gnomad AFR exome AF: 0.0538

Gnomad AMR exome AF: 0.00330

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00162 AC: 2373 AN: 1461752 Hom.: 45 Cov.: 32 AF XY: 0.00145 AC XY: 1055 AN XY: 727190

Gnomad4 AFR exome AF: 0.0545

Gnomad4 AMR exome AF: 0.00389

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000102

Gnomad4 OTH exome AF: 0.00373

GnomAD4 genome AF: 0.0150 AC: 2287 AN: 152240 Hom.: 49 Cov.: 33 AF XY: 0.0148 AC XY: 1100 AN XY: 74428

Gnomad4 AFR AF: 0.0516

Gnomad4 AMR AF: 0.00706

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00284 Hom.: 14

Bravo AF: 0.0176

ESP6500AA AF: 0.0515 AC: 227

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00492 AC: 597

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.15
Sift	Benign	0.036	D
Sift4G	Benign	0.13	T
Polyphen		0.83	P
Vest4		0.17
MVP		0.75
MPC		0.52
ClinPred		0.048	T
GERP RS		4.7
Varity_R		0.29
gMVP		0.62

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: rs734852; hg19: chr1-27720967;