1-27394569-C-T

Variant names:

• chr1-27394569-C-T
• rs2230880
• NM_005281.4:c.771C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_005281.4(GPR3):​c.771C>T​(p.Ala257Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,614,168 control chromosomes in the GnomAD database, including 185 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 0.0098 (15 hom., cov: 33)
  • Exomes 𝑓: 0.013 (170 hom.)
• Consequence: GPR3 NM_005281.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.68
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-4.68 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0133 (19470/1461852) while in subpopulation NFE AF = 0.0154 (17142/1112000). AF 95% confidence interval is 0.0152. There are 170 homozygotes in GnomAdExome4. There are 9613 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005281.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR3	NM_005281.4	MANE Select	c.771C>T	p.Ala257Ala	synonymous	Exon 2 of 2	NP_005272.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR3	ENST00000374024.4	TSL:1 MANE Select	c.771C>T	p.Ala257Ala	synonymous	Exon 2 of 2	ENSP00000363136.3
	GPR3	ENST00000924879.1		c.771C>T	p.Ala257Ala	synonymous	Exon 2 of 2	ENSP00000594938.1

Frequencies

GnomAD3 genomes AF: 0.00980 AC: 1491 AN: 152198 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00798

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00894

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0154

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00968 AC: 2431 AN: 251024 AF XY: 0.00984

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.00683

Gnomad ASJ exome AF: 0.0194

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00698

Gnomad NFE exome AF: 0.0147

Gnomad OTH exome AF: 0.0116

GnomAD4 exome AF: 0.0133 AC: 19470 AN: 1461852 Hom.: 170 Cov.: 32 AF XY: 0.0132 AC XY: 9613 AN XY: 727230

African (AFR) AF: 0.00197 AC: 66 AN: 33480

American (AMR) AF: 0.00736 AC: 329 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 519 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00291 AC: 251 AN: 86258

European-Finnish (FIN) AF: 0.00693 AC: 370 AN: 53392

Middle Eastern (MID) AF: 0.0111 AC: 64 AN: 5768

European-Non Finnish (NFE) AF: 0.0154 AC: 17142 AN: 1112000

Other (OTH) AF: 0.0121 AC: 728 AN: 60396

GnomAD4 genome AF: 0.00979 AC: 1491 AN: 152316 Hom.: 15 Cov.: 33 AF XY: 0.00943 AC XY: 702 AN XY: 74482

African (AFR) AF: 0.00274 AC: 114 AN: 41568

American (AMR) AF: 0.00797 AC: 122 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4822

European-Finnish (FIN) AF: 0.00894 AC: 95 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0154 AC: 1048 AN: 68024

Other (OTH) AF: 0.0123 AC: 26 AN: 2114

Alfa AF: 0.0116 Hom.: 10

Bravo AF: 0.00960

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0172

EpiControl AF: 0.0155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.4
DANN	Benign	0.89
PhyloP100		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs2230880; hg19: chr1-27721073; COSMIC: COSV64994787; COSMIC: COSV64994787;