rs2230344

Positions:

• chr3-98532142-C-T

Variant summary

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

The NM_005290.4(GPR15):​c.109C>T​(p.Pro37Ser) variant causes a missense change. The variant allele was found at a frequency of 0.16 in 1,613,950 control chromosomes in the GnomAD database, including 24,252 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 0.14 (2066 hom., cov: 32)
  • Exomes 𝑓: 0.16 (22186 hom.)
• Consequence: GPR15 NM_005290.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.02

Genes affected

GPR15 (HGNC:4469): (G protein-coupled receptor 15) This gene encodes a G protein-coupled receptor that acts as a chemokine receptor for human immunodeficiency virus type 1 and 2. The encoded protein localizes to the cell membrane. [provided by RefSeq, Nov 2012]

ENSG00000285635 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018767416).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR15	NM_005290.4	c.109C>T	p.Pro37Ser	missense_variant	1/1	ENST00000284311.5	NP_005281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR15	ENST00000284311.5	c.109C>T	p.Pro37Ser	missense_variant	1/1	6	NM_005290.4	ENSP00000284311.3
ENSG00000285635	ENST00000512905.6	n.*71-10700G>A		intron_variant		5		ENSP00000425880.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21567 AN: 152054 Hom.: 2068 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.143

GnomAD3 exomes AF: 0.201 AC: 50481 AN: 251398 Hom.: 6597 AF XY: 0.198 AC XY: 26897 AN XY: 135870

Gnomad AFR exome AF: 0.0466

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.390

Gnomad SAS exome AF: 0.228

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.162 AC: 237408 AN: 1461778 Hom.: 22186 Cov.: 35 AF XY: 0.164 AC XY: 119407 AN XY: 727218

Gnomad4 AFR exome AF: 0.0440

Gnomad4 AMR exome AF: 0.365

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.361

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.142 AC: 21563 AN: 152172 Hom.: 2066 Cov.: 32 AF XY: 0.147 AC XY: 10959 AN XY: 74380

Gnomad4 AFR AF: 0.0495

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.141

Alfa AF: 0.157 Hom.: 4991

Bravo AF: 0.148

TwinsUK AF: 0.138 AC: 513

ALSPAC AF: 0.149 AC: 574

ESP6500AA AF: 0.0508 AC: 224

ESP6500EA AF: 0.152 AC: 1304

ExAC AF: 0.191 AC: 23185

Asia WGS AF: 0.213 AC: 737 AN: 3478

EpiCase AF: 0.158

EpiControl AF: 0.156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-7.6	D
REVEL	Benign	0.13
Sift	Benign	0.056	T
Sift4G	Benign	0.20	T
Polyphen		0.21	B
Vest4		0.084
MPC		0.082
ClinPred		0.048	T
GERP RS		3.9
Varity_R		0.32
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2230344; hg19: chr3-98250986; COSMIC: COSV52520581;