chr3-46357717-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
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 (★).
Frequency
Genomes: 𝑓 0.12 ( 1287 hom., cov: 32)
Exomes 𝑓: 0.094 ( 7970 hom. )
Consequence
CCR2
NM_001123396.4 missense
NM_001123396.4 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: 1.13
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 -14 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]. Clinvar id is 8267.Status of the report is criteria_provided_single_submitter, 1 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 | UniProt |
---|---|---|---|---|---|---|---|
CCR2 | NM_001123396.4 | c.190G>A | p.Val64Ile | missense_variant | 2/2 | ENST00000445132.3 | |
CCR2 | NM_001123041.3 | c.190G>A | p.Val64Ile | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCR2 | ENST00000445132.3 | c.190G>A | p.Val64Ile | missense_variant | 2/2 | 1 | NM_001123396.4 | P2 | |
CCR2 | ENST00000400888.2 | c.190G>A | p.Val64Ile | missense_variant | 1/2 | 1 | A2 | ||
CCR2 | ENST00000421659.1 | c.190G>A | p.Val64Ile | missense_variant | 3/3 | 4 | |||
CCR2 | ENST00000465202.1 | n.315-400G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.121 AC: 18420AN: 151958Hom.: 1285 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.127 AC: 31797AN: 251286Hom.: 2499 AF XY: 0.121 AC XY: 16401AN XY: 135828
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GnomAD4 exome AF: 0.0943 AC: 137839AN: 1461864Hom.: 7970 Cov.: 32 AF XY: 0.0946 AC XY: 68798AN XY: 727236
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GnomAD4 genome ? AF: 0.121 AC: 18445AN: 152076Hom.: 1287 Cov.: 32 AF XY: 0.123 AC XY: 9115AN XY: 74344
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285
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271
ESP6500AA
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495
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659
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15351
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638
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CCR2-related disorder Benign:1
Benign, criteria provided, single submitter | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T;.
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;N
MutationTaster
Benign
P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
0.079
.;B;.;B
Vest4
MPC
0.20
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at