Genetic Variant CCR5:c.-11-344_-11-342delCAA (chr3-46372528-CACA-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001394783.1(CCR5):c.-11-344_-11-342delCAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 167,440 control chromosomes in the GnomAD database, including 8,282 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7686 hom., cov: 0)

Exomes 𝑓: 0.26 ( 596 hom. )

Consequence

CCR5
NM_001394783.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR5	NM_001394783.1 link	c.-11-344_-11-342delCAA		intron_variant	Intron 1 of 1	ENST00000292303.5	NP_001381712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR5	ENST00000292303.5 link	c.-11-363_-11-361delACA		intron_variant	Intron 1 of 1	1	NM_001394783.1	ENSP00000292303.4		P51681

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45327

AN:

151276

Hom.:

7685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.552

Gnomad SAS

AF:

0.414

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.353

Gnomad OTH

AF:

0.347

GnomAD4 exome

AF:

0.260

AC:

4167

AN:

16046

Hom.:

596

AF XY:

0.256

AC XY:

2382

AN XY:

9296

show subpopulations

African (AFR)

AF:

0.0698

AC:

AN:

258

American (AMR)

AF:

0.313

AC:

551

AN:

1758

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

AN:

230

East Asian (EAS)

AF:

0.409

AC:

212

AN:

518

South Asian (SAS)

AF:

0.307

AC:

407

AN:

1326

European-Finnish (FIN)

AF:

0.165

AC:

AN:

436

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.245

AC:

2651

AN:

10804

Other (OTH)

AF:

0.274

AC:

188

AN:

686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

135

271

406

542

677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.299

AC:

45334

AN:

151394

Hom.:

7686

Cov.:

AF XY:

0.304

AC XY:

22439

AN XY:

73918

show subpopulations

African (AFR)

AF:

0.127

AC:

5239

AN:

41352

American (AMR)

AF:

0.376

AC:

5728

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1323

AN:

3466

East Asian (EAS)

AF:

0.551

AC:

2801

AN:

5080

South Asian (SAS)

AF:

0.415

AC:

1985

AN:

4782

European-Finnish (FIN)

AF:

0.306

AC:

3195

AN:

10428

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.353

AC:

23923

AN:

67766

Other (OTH)

AF:

0.344

AC:

719

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1498

2996

4493

5991

7489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.108

Hom.:

170

Bravo

AF:

0.298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over