chr3-46373570-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1
The NM_001394783.1(CCR5):c.668G>A(p.Arg223Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,613,554 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.0027 ( 7 hom., cov: 32)
Exomes 𝑓: 0.0028 ( 93 hom. )
Consequence
CCR5
NM_001394783.1 missense
NM_001394783.1 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: 0.179
Genes affected
CCR5 (HGNC:1606): (C-C motif chemokine receptor 5) This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. This protein is expressed by T cells and macrophages, and is known to be an important co-receptor for macrophage-tropic virus, including HIV, to enter host cells. Defective alleles of this gene have been associated with the HIV infection resistance. The ligands of this receptor include monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein 1 alpha (MIP-1 alpha), macrophage inflammatory protein 1 beta (MIP-1 beta) and regulated on activation normal T expressed and secreted protein (RANTES). Expression of this gene was also detected in a promyeloblastic cell line, suggesting that this protein may play a role in granulocyte lineage proliferation and differentiation. This gene is located at the chemokine receptor gene cluster region. An allelic polymorphism in this gene results in both functional and non-functional alleles; the reference genome represents the functional allele. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0027464628).
BP6
?
Variant 3-46373570-G-A is Benign according to our data. Variant chr3-46373570-G-A is described in ClinVar as [Benign]. Clinvar id is 8186.Status of the report is no_assertion_criteria_provided, 0 stars.
BA1
?
GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0595 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCR5 | NM_001394783.1 | c.668G>A | p.Arg223Gln | missense_variant | 2/2 | ENST00000292303.5 | |
CCR5AS | NR_125406.1 | n.392-2153C>T | intron_variant, non_coding_transcript_variant | ||||
CCR5 | NM_000579.4 | c.668G>A | p.Arg223Gln | missense_variant | 3/3 | ||
CCR5 | NM_001100168.2 | c.668G>A | p.Arg223Gln | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCR5 | ENST00000292303.5 | c.668G>A | p.Arg223Gln | missense_variant | 2/2 | 1 | NM_001394783.1 | P1 | |
CCR5AS | ENST00000701879.1 | n.174-2153C>T | intron_variant, non_coding_transcript_variant | ||||||
CCR5 | ENST00000445772.1 | c.668G>A | p.Arg223Gln | missense_variant | 1/1 | P1 | |||
CCR5AS | ENST00000451485.2 | n.392-2153C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00271 AC: 412AN: 152076Hom.: 7 Cov.: 32
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GnomAD3 exomes AF: 0.00492 AC: 1235AN: 250954Hom.: 27 AF XY: 0.00461 AC XY: 625AN XY: 135616
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GnomAD4 exome AF: 0.00275 AC: 4021AN: 1461360Hom.: 93 Cov.: 32 AF XY: 0.00279 AC XY: 2025AN XY: 726948
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GnomAD4 genome ? AF: 0.00272 AC: 414AN: 152194Hom.: 7 Cov.: 32 AF XY: 0.00302 AC XY: 225AN XY: 74418
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
CCR5 POLYMORPHISM, ORIENTAL 2 Benign:1
Benign, no assertion criteria provided | literature only | OMIM | Jul 01, 1997 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
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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