rs1800941

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_001394783.1(CCR5):ā€‹c.225T>Cā€‹(p.Ser75Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,614,052 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0018 ( 1 hom., cov: 32)
Exomes š‘“: 0.00015 ( 0 hom. )

Consequence

CCR5
NM_001394783.1 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.83
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP7
Synonymous conserved (PhyloP=-2.84 with no splicing effect.
BS2
High AC in GnomAd4 at 267 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCR5NM_001394783.1 linkuse as main transcriptc.225T>C p.Ser75Ser synonymous_variant 2/2 ENST00000292303.5 NP_001381712.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCR5ENST00000292303.5 linkuse as main transcriptc.225T>C p.Ser75Ser synonymous_variant 2/21 NM_001394783.1 ENSP00000292303.4 P51681
CCR5ENST00000445772.1 linkuse as main transcriptc.225T>C p.Ser75Ser synonymous_variant 1/16 ENSP00000404881.1 P51681
CCR5ASENST00000451485.2 linkuse as main transcriptn.392-1710A>G intron_variant 3
CCR5ASENST00000701879.1 linkuse as main transcriptn.174-1710A>G intron_variant

Frequencies

GnomAD3 genomes
AF:
0.00175
AC:
267
AN:
152212
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00625
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.000477
AC:
120
AN:
251324
Hom.:
0
AF XY:
0.000302
AC XY:
41
AN XY:
135816
show subpopulations
Gnomad AFR exome
AF:
0.00701
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000152
AC:
222
AN:
1461722
Hom.:
0
Cov.:
32
AF XY:
0.000127
AC XY:
92
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.00591
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000248
GnomAD4 genome
AF:
0.00175
AC:
267
AN:
152330
Hom.:
1
Cov.:
32
AF XY:
0.00160
AC XY:
119
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.00623
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.000931
Hom.:
0
Bravo
AF:
0.00188
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.59
DANN
Benign
0.57

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: rs1800941; hg19: chr3-46414618; API