rs11586015

Positions:

• chr1-27393849-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The ENST00000374024.4(GPR3):​c.51C>A​(p.Gly17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 1,579,590 control chromosomes in the GnomAD database, including 400 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.

• Frequency:
  • Genomes: 𝑓 0.014 (23 hom., cov: 33)
  • Exomes 𝑓: 0.021 (377 hom.)
• Consequence: GPR3 ENST00000374024.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=0.051 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.014 (2137/152310) while in subpopulation NFE AF= 0.0218 (1484/68012). AF 95% confidence interval is 0.0209. There are 23 homozygotes in gnomad4. There are 978 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR3	NM_005281.4	c.51C>A	p.Gly17=	synonymous_variant	2/2	ENST00000374024.4	NP_005272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR3	ENST00000374024.4	c.51C>A	p.Gly17=	synonymous_variant	2/2	1	NM_005281.4	ENSP00000363136	P1

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2136 AN: 152192 Hom.: 23 Cov.: 33

Gnomad AFR AF: 0.00425

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00602

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0218

Gnomad OTH AF: 0.0186

GnomAD3 exomes AF: 0.0141 AC: 3275 AN: 232144 Hom.: 34 AF XY: 0.0147 AC XY: 1837 AN XY: 125364

Gnomad AFR exome AF: 0.00417

Gnomad AMR exome AF: 0.0143

Gnomad ASJ exome AF: 0.0243

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00273

Gnomad FIN exome AF: 0.00586

Gnomad NFE exome AF: 0.0214

Gnomad OTH exome AF: 0.0178

GnomAD4 exome AF: 0.0205 AC: 29295 AN: 1427280 Hom.: 377 Cov.: 31 AF XY: 0.0198 AC XY: 13984 AN XY: 705452

Gnomad4 AFR exome AF: 0.00390

Gnomad4 AMR exome AF: 0.0144

Gnomad4 ASJ exome AF: 0.0234

Gnomad4 EAS exome AF: 0.0000511

Gnomad4 SAS exome AF: 0.00274

Gnomad4 FIN exome AF: 0.00581

Gnomad4 NFE exome AF: 0.0240

Gnomad4 OTH exome AF: 0.0215

GnomAD4 genome AF: 0.0140 AC: 2137 AN: 152310 Hom.: 23 Cov.: 33 AF XY: 0.0131 AC XY: 978 AN XY: 74458

Gnomad4 AFR AF: 0.00423

Gnomad4 AMR AF: 0.0179

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00602

Gnomad4 NFE AF: 0.0218

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0210 Hom.: 41

Bravo AF: 0.0145

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.0
DANN	Benign	0.83

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: rs11586015; hg19: chr1-27720353;