dbSNP rs1799865: CCR2:p.Asn260Asn (chr3-46358307-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001123396.4(CCR2):c.780T>C(p.Asn260Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,613,876 control chromosomes in the GnomAD database, including 80,922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.32 ( 7841 hom., cov: 32)

Exomes 𝑓: 0.31 ( 73081 hom. )

Consequence

CCR2
NM_001123396.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.70

Publications

48 publications found

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 was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-46358307-T-C is Benign according to our data. Variant chr3-46358307-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059948.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123396.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR2	NM_001123396.4	MANE Select	c.780T>C	p.Asn260Asn	synonymous	Exon 2 of 2	NP_001116868.1
	CCR2	NM_001123041.3		c.780T>C	p.Asn260Asn	synonymous	Exon 2 of 3	NP_001116513.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CCR2	ENST00000445132.3	TSL:1 MANE Select	c.780T>C	p.Asn260Asn	synonymous	Exon 2 of 2	ENSP00000399285.2
CCR2	ENST00000400888.2	TSL:1	c.780T>C	p.Asn260Asn	synonymous	Exon 1 of 2	ENSP00000383681.2
CCR2	ENST00000465202.1	TSL:5	n.505T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48628

AN:

151928

Hom.:

7823

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.337

GnomAD2 exomes

AF:

0.320

AC:

80079

AN:

250390

AF XY:

0.323

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.263

Gnomad EAS exome

AF:

0.328

Gnomad FIN exome

AF:

0.297

Gnomad NFE exome

AF:

0.313

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.314

AC:

459207

AN:

1461830

Hom.:

73081

Cov.:

AF XY:

0.316

AC XY:

229821

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.338

AC:

11310

AN:

33480

American (AMR)

AF:

0.325

AC:

14514

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

6814

AN:

26136

East Asian (EAS)

AF:

0.277

AC:

11002

AN:

39700

South Asian (SAS)

AF:

0.366

AC:

31547

AN:

86258

European-Finnish (FIN)

AF:

0.291

AC:

15567

AN:

53418

Middle Eastern (MID)

AF:

0.389

AC:

2242

AN:

5768

European-Non Finnish (NFE)

AF:

0.312

AC:

346746

AN:

1111952

Other (OTH)

AF:

0.322

AC:

19465

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

20163

40327

60490

80654

100817

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11394

22788

34182

45576

56970

<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:

0.320

AC:

48665

AN:

152046

Hom.:

7841

Cov.:

AF XY:

0.322

AC XY:

23956

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.332

AC:

13749

AN:

41438

American (AMR)

AF:

0.354

AC:

5404

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

934

AN:

3468

East Asian (EAS)

AF:

0.312

AC:

1619

AN:

5182

South Asian (SAS)

AF:

0.355

AC:

1707

AN:

4814

European-Finnish (FIN)

AF:

0.291

AC:

3081

AN:

10582

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.310

AC:

21081

AN:

67962

Other (OTH)

AF:

0.334

AC:

704

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1691

3382

5073

6764

8455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.310

Hom.:

3368

Bravo

AF:

0.323

Asia WGS

AF:

0.307

AC:

1066

AN:

3478

EpiCase

AF:

0.332

EpiControl

AF:

0.324

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CCR2-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.2

(source)

DANN

Benign

0.30

PhyloP100

1.7

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over