1-27394569-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.68
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. gnomad4_exome 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 gnomad4_exome. There are 9613 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPR3NM_005281.4 linkuse as main transcriptc.771C>T p.Ala257Ala synonymous_variant 2/2 ENST00000374024.4 NP_005272.1 P46089F1DAM5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPR3ENST00000374024.4 linkuse as main transcriptc.771C>T p.Ala257Ala synonymous_variant 2/21 NM_005281.4 ENSP00000363136.3 P46089

Frequencies

GnomAD3 genomes
AF:
0.00980
AC:
1491
AN:
152198
Hom.:
15
Cov.:
33
show subpopulations
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
GnomAD3 exomes
AF:
0.00968
AC:
2431
AN:
251024
Hom.:
14
AF XY:
0.00984
AC XY:
1335
AN XY:
135674
show subpopulations
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 SAS exome
AF:
0.00265
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
show subpopulations
Gnomad4 AFR exome
AF:
0.00197
Gnomad4 AMR exome
AF:
0.00736
Gnomad4 ASJ exome
AF:
0.0199
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00291
Gnomad4 FIN exome
AF:
0.00693
Gnomad4 NFE exome
AF:
0.0154
Gnomad4 OTH exome
AF:
0.0121
GnomAD4 genome
AF:
0.00979
AC:
1491
AN:
152316
Hom.:
15
Cov.:
33
AF XY:
0.00943
AC XY:
702
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.00274
Gnomad4 AMR
AF:
0.00797
Gnomad4 ASJ
AF:
0.0216
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.00894
Gnomad4 NFE
AF:
0.0154
Gnomad4 OTH
AF:
0.0123
Alfa
AF:
0.0112
Hom.:
7
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 v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
3.4
DANN
Benign
0.89
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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