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GeneBe

3-46358307-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001123396.4(CCR2):c.780T>C(p.Asn260=) 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 (★).

Frequency

Genomes: 𝑓 0.32 ( 7841 hom., cov: 32)
Exomes 𝑓: 0.31 ( 73081 hom. )

Consequence

CCR2
NM_001123396.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.70
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-46358307-T-C is Benign according to our data. Variant chr3-46358307-T-C is described in ClinVar as [Benign]. Clinvar id is 3059948.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.7 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCR2NM_001123396.4 linkuse as main transcriptc.780T>C p.Asn260= synonymous_variant 2/2 ENST00000445132.3
CCR2NM_001123041.3 linkuse as main transcriptc.780T>C p.Asn260= synonymous_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCR2ENST00000445132.3 linkuse as main transcriptc.780T>C p.Asn260= synonymous_variant 2/21 NM_001123396.4 P2P41597-2
CCR2ENST00000400888.2 linkuse as main transcriptc.780T>C p.Asn260= synonymous_variant 1/21 A2P41597-1
CCR2ENST00000465202.1 linkuse as main transcriptn.505T>C non_coding_transcript_exon_variant 2/25

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.320
AC:
48628
AN:
151928
Hom.:
7823
Cov.:
32
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
GnomAD3 exomes
AF:
0.320
AC:
80079
AN:
250390
Hom.:
13119
AF XY:
0.323
AC XY:
43790
AN XY:
135670
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 SAS exome
AF:
0.363
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.:
41
AF XY:
0.316
AC XY:
229821
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.338
Gnomad4 AMR exome
AF:
0.325
Gnomad4 ASJ exome
AF:
0.261
Gnomad4 EAS exome
AF:
0.277
Gnomad4 SAS exome
AF:
0.366
Gnomad4 FIN exome
AF:
0.291
Gnomad4 NFE exome
AF:
0.312
Gnomad4 OTH exome
AF:
0.322
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.320
AC:
48665
AN:
152046
Hom.:
7841
Cov.:
32
AF XY:
0.322
AC XY:
23956
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.332
Gnomad4 AMR
AF:
0.354
Gnomad4 ASJ
AF:
0.269
Gnomad4 EAS
AF:
0.312
Gnomad4 SAS
AF:
0.355
Gnomad4 FIN
AF:
0.291
Gnomad4 NFE
AF:
0.310
Gnomad4 OTH
AF:
0.334
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

CCR2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This 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 v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
Cadd
Benign
2.2
Dann
Benign
0.30

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.

Other links and lift over

dbSNP: rs1799865; hg19: chr3-46399798; COSMIC: COSV52747792; COSMIC: COSV52747792; API