rs1799864

Positions:

chr3-46357717-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001123396.4(CCR2):c.190G>A(p.Val64Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,613,940 control chromosomes in the GnomAD database, including 9,257 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,protective (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1287 hom., cov: 32)

Exomes 𝑓: 0.094 ( 7970 hom. )

Consequence

CCR2
NM_001123396.4 missense

Scores

Clinical Significance

Benign; protective no assertion criteria provided B:2

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

CCR2 (HGNC:1603): (C-C motif chemokine receptor 2) The protein encoded by this gene is a receptor for monocyte chemoattractant protein-1, a chemokine which specifically mediates monocyte chemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis as well as in the inflammatory response against tumors. The encoded protein mediates agonist-dependent calcium mobilization and inhibition of adenylyl cyclase. This protein can also be a coreceptor with CD4 for HIV-1 infection. This gene is located in the chemokine receptor gene cluster region of chromosome 3. [provided by RefSeq, Aug 2017]

CCR2 links:

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 (MetaRNN=0.0017913282).

BP6

Variant 3-46357717-G-A is Benign according to our data. Variant chr3-46357717-G-A is described in ClinVar as [Benign, protective]. Clinvar id is 8267.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR2	NM_001123396.4 linkuse as main transcript	c.190G>A	p.Val64Ile	missense_variant	2/2	ENST00000445132.3	NP_001116868.1
CCR2	NM_001123041.3 linkuse as main transcript	c.190G>A	p.Val64Ile	missense_variant	2/3		NP_001116513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR2	ENST00000445132.3 linkuse as main transcript	c.190G>A	p.Val64Ile	missense_variant	2/2	1	NM_001123396.4	ENSP00000399285	P2	P41597-2
CCR2	ENST00000400888.2 linkuse as main transcript	c.190G>A	p.Val64Ile	missense_variant	1/2	1		ENSP00000383681	A2	P41597-1
CCR2	ENST00000421659.1 linkuse as main transcript	c.190G>A	p.Val64Ile	missense_variant	3/3	4		ENSP00000396736
CCR2	ENST00000465202.1 linkuse as main transcript	n.315-400G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18420

AN:

151958

Hom.:

1285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0632

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.0900

Gnomad OTH

AF:

0.132

GnomAD3 exomes

AF:

0.127

AC:

31797

AN:

251286

Hom.:

2499

AF XY:

0.121

AC XY:

16401

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.204

Gnomad SAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.0661

Gnomad NFE exome

AF:

0.0942

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.0943

AC:

137839

AN:

1461864

Hom.:

7970

Cov.:

AF XY:

0.0946

AC XY:

68798

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.223

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.244

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.0710

Gnomad4 NFE exome

AF:

0.0803

Gnomad4 OTH exome

AF:

0.102

GnomAD4 genome

AF:

0.121

AC:

18445

AN:

152076

Hom.:

1287

Cov.:

AF XY:

0.123

AC XY:

9115

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.125

Gnomad4 EAS

AF:

0.212

Gnomad4 SAS

AF:

0.121

Gnomad4 FIN

AF:

0.0632

Gnomad4 NFE

AF:

0.0900

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.105

Hom.:

1496

Bravo

AF:

0.132

TwinsUK

AF:

0.0769

AC:

285

ALSPAC

AF:

0.0703

AC:

271

ESP6500AA

AF:

0.158

AC:

495

ESP6500EA

AF:

0.0920

AC:

659

ExAC

AF:

0.126

AC:

15351

Asia WGS

AF:

0.184

AC:

638

AN:

3478

EpiCase

AF:

0.0955

EpiControl

AF:

0.0912

ClinVar

Significance: Benign; protective

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CCR2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Susceptibility to HIV infection

Benign:1

protective, no assertion criteria provided

literature only

OMIM

May 18, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.031

.;T;.;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.69

T;T;T;.

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.78

N;N;.;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.48

N;N;N;N

REVEL

Benign

0.030

Sift

Benign

0.33

T;T;T;T

Sift4G

Benign

0.38

T;T;T;T

Polyphen

0.079

.;B;.;B

Vest4

0.080

MPC

0.20

ClinPred

0.0028

GERP RS

1.6

Varity_R

0.045

gMVP

0.10

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over