3-46373066-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001394783.1(CCR5):c.164T>A(p.Leu55Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0193 in 1,614,198 control chromosomes in the GnomAD database, including 349 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: 𝑓 0.014 ( 29 hom., cov: 32)

Exomes 𝑓: 0.020 ( 320 hom. )

Consequence

CCR5
NM_001394783.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.26

Publications

33 publications found

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]

CCR5 links:

CCR5AS (HGNC:54398): (CCR5 antisense RNA)

CCR5AS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008668691).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0141 (2142/152324) while in subpopulation NFE AF = 0.0224 (1523/68028). AF 95% confidence interval is 0.0215. There are 29 homozygotes in GnomAd4. There are 962 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2142 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394783.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CCR5	NM_001394783.1	MANE Select	c.164T>A	p.Leu55Gln	missense	Exon 2 of 2	NP_001381712.1
CCR5AS	NR_125406.2	MANE Select	n.399-1649A>T		intron	N/A
CCR5	NM_000579.4		c.164T>A	p.Leu55Gln	missense	Exon 3 of 3	NP_000570.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CCR5	ENST00000292303.5	TSL:1 MANE Select	c.164T>A	p.Leu55Gln	missense	Exon 2 of 2	ENSP00000292303.4
CCR5AS	ENST00000451485.3	TSL:3 MANE Select	n.399-1649A>T		intron	N/A
CCR5	ENST00000445772.1	TSL:6	c.164T>A	p.Leu55Gln	missense	Exon 1 of 1	ENSP00000404881.1

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2144

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00528

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0183

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0224

Gnomad OTH

AF:

0.0138

GnomAD2 exomes

AF:

0.0136

AC:

3419

AN:

251422

AF XY:

0.0135

show subpopulations

Gnomad AFR exome

AF:

0.00431

Gnomad AMR exome

AF:

0.0144

Gnomad ASJ exome

AF:

0.0192

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.0221

Gnomad OTH exome

AF:

0.0165

GnomAD4 exome

AF:

0.0198

AC:

28987

AN:

1461874

Hom.:

320

Cov.:

AF XY:

0.0194

AC XY:

14119

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00320

AC:

107

AN:

33480

American (AMR)

AF:

0.0149

AC:

668

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

489

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.000661

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00165

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0238

AC:

26476

AN:

1111992

Other (OTH)

AF:

0.0172

AC:

1041

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1680

3361

5041

6722

8402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

992

1984

2976

3968

4960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0141

AC:

2142

AN:

152324

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

962

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00527

AC:

219

AN:

41580

American (AMR)

AF:

0.0183

AC:

280

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0224

AC:

1523

AN:

68028

Other (OTH)

AF:

0.0137

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

113

226

340

453

566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0212

Hom.:

Bravo

AF:

0.0152

TwinsUK

AF:

0.0264

AC:

ALSPAC

AF:

0.0265

AC:

102

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.0235

AC:

202

ExAC

AF:

0.0127

AC:

1545

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0237

EpiControl

AF:

0.0253

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.0087

MetaSVM

Uncertain

-0.058

MutationAssessor

Pathogenic

4.2

PhyloP100

6.3

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-5.4

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.52

ClinPred

0.070

GERP RS

5.4

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.98

gMVP

0.77

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over