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GeneBe

rs333

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001394783.1(CCR5):c.554_585del(p.Ser185IlefsTer32) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 1,613,870 control chromosomes in the GnomAD database, including 8,868 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 553 hom., cov: 31)
Exomes 𝑓: 0.10 ( 8315 hom. )

Consequence

CCR5
NM_001394783.1 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:2

Conservation

PhyloP100: 0.894
Variant links:
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]
CCR5AS (HGNC:54398): (CCR5 antisense RNA)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCR5NM_001394783.1 linkuse as main transcriptc.554_585del p.Ser185IlefsTer32 frameshift_variant 2/2 ENST00000292303.5
CCR5ASNR_125406.1 linkuse as main transcriptn.392-2067_392-2036del intron_variant, non_coding_transcript_variant
CCR5NM_000579.4 linkuse as main transcriptc.554_585del p.Ser185IlefsTer32 frameshift_variant 3/3
CCR5NM_001100168.2 linkuse as main transcriptc.554_585del p.Ser185IlefsTer32 frameshift_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCR5ENST00000292303.5 linkuse as main transcriptc.554_585del p.Ser185IlefsTer32 frameshift_variant 2/21 NM_001394783.1 P1
CCR5ASENST00000701879.1 linkuse as main transcriptn.174-2067_174-2036del intron_variant, non_coding_transcript_variant
CCR5ENST00000445772.1 linkuse as main transcriptc.554_585del p.Ser185IlefsTer32 frameshift_variant 1/1 P1
CCR5ASENST00000451485.2 linkuse as main transcriptn.392-2067_392-2036del intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0718
AC:
10911
AN:
152034
Hom.:
553
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0204
Gnomad AMI
AF:
0.180
Gnomad AMR
AF:
0.0370
Gnomad ASJ
AF:
0.130
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.0135
Gnomad FIN
AF:
0.135
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.107
Gnomad OTH
AF:
0.0483
GnomAD3 exomes
AF:
0.0743
AC:
18640
AN:
251006
Hom.:
966
AF XY:
0.0745
AC XY:
10108
AN XY:
135678
show subpopulations
Gnomad AFR exome
AF:
0.0192
Gnomad AMR exome
AF:
0.0293
Gnomad ASJ exome
AF:
0.129
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0160
Gnomad FIN exome
AF:
0.134
Gnomad NFE exome
AF:
0.108
Gnomad OTH exome
AF:
0.0726
GnomAD4 exome
AF:
0.100
AC:
146811
AN:
1461718
Hom.:
8315
AF XY:
0.0983
AC XY:
71450
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.0154
Gnomad4 AMR exome
AF:
0.0303
Gnomad4 ASJ exome
AF:
0.131
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0171
Gnomad4 FIN exome
AF:
0.131
Gnomad4 NFE exome
AF:
0.115
Gnomad4 OTH exome
AF:
0.0877
GnomAD4 genome
AF:
0.0717
AC:
10914
AN:
152152
Hom.:
553
Cov.:
31
AF XY:
0.0707
AC XY:
5259
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.0203
Gnomad4 AMR
AF:
0.0370
Gnomad4 ASJ
AF:
0.130
Gnomad4 EAS
AF:
0.000579
Gnomad4 SAS
AF:
0.0141
Gnomad4 FIN
AF:
0.135
Gnomad4 NFE
AF:
0.107
Gnomad4 OTH
AF:
0.0478
Alfa
AF:
0.0929
Hom.:
121
Asia WGS
AF:
0.0120
AC:
43
AN:
3478
EpiCase
AF:
0.0915
EpiControl
AF:
0.0970

ClinVar

Significance: Benign
Submissions summary: Benign:4Other:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Susceptibility to HIV infection Benign:1
protective, no assertion criteria providedliterature onlyOMIMDec 01, 2008- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 22, 2019- -
Resistance to hepatitis C virus Benign:1
protective, no assertion criteria providedliterature onlyOMIMDec 01, 2008- -
CCR5-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMay 10, 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). -
West Nile virus, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMDec 01, 2008- -
Multiple sclerosis modifier of disease progression Other:1
risk factor, no assertion criteria providedliterature onlyOMIMDec 01, 2008- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs333; hg19: chr3-46414943; API