Genetic Variant CCR2:p.Val52Val (chr3-46357683-G-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001123396.4(CCR2):c.156G>T(p.Val52Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00884 in 1,614,122 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 91 hom. )

Consequence

CCR2
NM_001123396.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.132

Publications

9 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 3-46357683-G-T is Benign according to our data. Variant chr3-46357683-G-T is described in ClinVar as Benign. ClinVar VariationId is 714233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.132 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR2	NM_001123396.4	MANE Select	c.156G>T	p.Val52Val	synonymous	Exon 2 of 2	NP_001116868.1	P41597-2
	CCR2	NM_001123041.3		c.156G>T	p.Val52Val	synonymous	Exon 2 of 3	NP_001116513.2	P41597-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCR2	ENST00000445132.3	TSL:1 MANE Select	c.156G>T	p.Val52Val	synonymous	Exon 2 of 2	ENSP00000399285.2	P41597-2
CCR2	ENST00000400888.2	TSL:1	c.156G>T	p.Val52Val	synonymous	Exon 1 of 2	ENSP00000383681.2	P41597-1
CCR2	ENST00000908302.1		c.156G>T	p.Val52Val	synonymous	Exon 2 of 2	ENSP00000578361.1

Frequencies

GnomAD3 genomes

AF:

0.00697

AC:

1061

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00472

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00643

Gnomad FIN

AF:

0.0185

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00988

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.00733

AC:

1843

AN:

251344

AF XY:

0.00785

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00202

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0184

Gnomad NFE exome

AF:

0.00935

Gnomad OTH exome

AF:

0.00847

GnomAD4 exome

AF:

0.00903

AC:

13203

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00909

AC XY:

6610

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

33480

American (AMR)

AF:

0.00210

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00107

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00776

AC:

669

AN:

86258

European-Finnish (FIN)

AF:

0.0165

AC:

883

AN:

53420

Middle Eastern (MID)

AF:

0.00433

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00993

AC:

11042

AN:

1111996

Other (OTH)

AF:

0.00685

AC:

414

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

888

1775

2663

3550

4438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.00697

AC:

1061

AN:

152246

Hom.:

Cov.:

AF XY:

0.00767

AC XY:

571

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00171

AC:

AN:

41534

American (AMR)

AF:

0.00471

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000772

AC:

AN:

5182

South Asian (SAS)

AF:

0.00643

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0185

AC:

196

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00988

AC:

672

AN:

68022

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

100

149

199

249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00866

Hom.:

Bravo

AF:

0.00567

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.00865

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

5.7

(source)

DANN

Benign

0.62

PhyloP100

0.13

PromoterAI

-0.033

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

Computational scores

Splicing

Publications

Other links and lift over