chr3-46370444-A-G
Variant names:
Variant summary
Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
Benign
The NM_000579.4(CCR5):c.-301+246A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 151,794 control chromosomes in the GnomAD database, including 18,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity,protective (no stars).
Frequency
Genomes: 𝑓 0.49 ( 18573 hom., cov: 30)
Consequence
CCR5
NM_000579.4 intron
NM_000579.4 intron
Scores
3
Clinical Significance
Conservation
PhyloP100: -0.587
Publications
128 publications found
Genes affected
CCR5AS (HGNC:54398): (CCR5 antisense RNA)
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]
Genome browser will be placed here
new If you want to explore the variant's impact on the transcript NM_000579.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000579.4. You can select a different transcript below to see updated ACMG assignments.
Frequencies
GnomAD3 genomes 0.491 AC: 74529AN: 151674Hom.: 18552 Cov.: 30 show subpopulations
GnomAD3 genomes
AF:
AC:
74529
AN:
151674
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.491 AC: 74586AN: 151794Hom.: 18573 Cov.: 30 AF XY: 0.496 AC XY: 36779AN XY: 74166 show subpopulations
GnomAD4 genome
AF:
AC:
74586
AN:
151794
Hom.:
Cov.:
30
AF XY:
AC XY:
36779
AN XY:
74166
show subpopulations
African (AFR)
AF:
AC:
23616
AN:
41378
American (AMR)
AF:
AC:
7025
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
AC:
1536
AN:
3460
East Asian (EAS)
AF:
AC:
3031
AN:
5152
South Asian (SAS)
AF:
AC:
2948
AN:
4820
European-Finnish (FIN)
AF:
AC:
4828
AN:
10492
Middle Eastern (MID)
AF:
AC:
166
AN:
292
European-Non Finnish (NFE)
AF:
AC:
29973
AN:
67914
Other (OTH)
AF:
AC:
1039
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1919
3838
5757
7676
9595
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
670
1340
2010
2680
3350
<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:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1859
AN:
3478
ClinVar
ClinVar submissions
View on ClinVar Significance:Conflicting classifications of pathogenicity; protective
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Acquired immunodeficiency syndrome, delayed progression to (1)
-
-
1
CCR5 PROMOTER POLYMORPHISM (1)
-
-
1
CCR5-related disorder (1)
-
-
-
Susceptibility to HIV infection (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.
Other links and lift over
dbSNP: rs1799987 ;
hg19: chr3-46411935;