Genetic Variant NM_005290.4:c.109C>T (chr3-98532142-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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.

Frequency

Genomes: 𝑓 0.14 ( 2066 hom., cov: 32)

Exomes 𝑓: 0.16 ( 22186 hom. )

Consequence

GPR15
NM_005290.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.02

Publications

24 publications found

Variant links:

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]

GPR15 links:

ENSG00000285635 (HGNC:):

ENSG00000285635 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPR15	NM_005290.4 link	c.109C>T	p.Pro37Ser	missense_variant	Exon 1 of 1	ENST00000284311.5	NP_005281.1	P49685B6V9G9B2R8H6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR15	ENST00000284311.5 link	c.109C>T	p.Pro37Ser	missense_variant	Exon 1 of 1	6	NM_005290.4	ENSP00000284311.3		P49685
ENSG00000285635	ENST00000512905.6 link	n.*71-10700G>A		intron_variant	Intron 3 of 3	5		ENSP00000425880.1		H0YA22

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21567

AN:

152054

Hom.:

2068

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.201

AC:

50481

AN:

251398

AF XY:

0.198

show subpopulations

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 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.:

AF XY:

0.164

AC XY:

119407

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.0440

AC:

1474

AN:

33480

American (AMR)

AF:

0.365

AC:

16322

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

3906

AN:

26136

East Asian (EAS)

AF:

0.361

AC:

14337

AN:

39698

South Asian (SAS)

AF:

0.230

AC:

19863

AN:

86256

European-Finnish (FIN)

AF:

0.131

AC:

6978

AN:

53420

Middle Eastern (MID)

AF:

0.197

AC:

1139

AN:

5768

European-Non Finnish (NFE)

AF:

0.147

AC:

163208

AN:

1111916

Other (OTH)

AF:

0.169

AC:

10181

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

11247

22493

33740

44986

56233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6082

12164

18246

24328

30410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.142

AC:

21563

AN:

152172

Hom.:

2066

Cov.:

AF XY:

0.147

AC XY:

10959

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0495

AC:

2058

AN:

41544

American (AMR)

AF:

0.265

AC:

4044

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

502

AN:

3472

East Asian (EAS)

AF:

0.371

AC:

1922

AN:

5174

South Asian (SAS)

AF:

0.223

AC:

1075

AN:

4812

European-Finnish (FIN)

AF:

0.136

AC:

1437

AN:

10582

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10122

AN:

67986

Other (OTH)

AF:

0.141

AC:

297

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

905

1811

2716

3622

4527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.153

Hom.:

6836

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

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.055

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.3

PhyloP100

5.0

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-7.6

REVEL

Benign

0.13

Sift

Benign

0.056

Sift4G

Benign

0.20

Polyphen

0.21

Vest4

0.084

MPC

0.082

ClinPred

0.048

GERP RS

3.9

PromoterAI

0.025

Neutral

(source)

Varity_R

0.32

gMVP

0.51

Mutation Taster

=79/21

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over