rs333

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001394783.1(CCR5):c.554_585delGTCAGTATCAATTCTGGAAGAATTTCCAGACA(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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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, single submitter B:4O:2

Conservation

PhyloP100: 0.894

Publications

205 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 -10 ACMG points.

BP6

Variant 3-46373452-TACAGTCAGTATCAATTCTGGAAGAATTTCCAG-T is Benign according to our data. Variant chr3-46373452-TACAGTCAGTATCAATTCTGGAAGAATTTCCAG-T is described in ClinVar as Benign. ClinVar VariationId is 8184.Status of the report is criteria_provided_single_submitter, 1 stars.

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 rank	MANE	Protein	UniProt
CCR5	NM_001394783.1 link	c.554_585delGTCAGTATCAATTCTGGAAGAATTTCCAGACA	p.Ser185IlefsTer32	frameshift_variant	Exon 2 of 2	ENST00000292303.5	NP_001381712.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR5	ENST00000292303.5 link	c.554_585delGTCAGTATCAATTCTGGAAGAATTTCCAGACA	p.Ser185IlefsTer32	frameshift_variant	Exon 2 of 2	1	NM_001394783.1	ENSP00000292303.4		P51681

Frequencies

GnomAD3 genomes

AF:

0.0718

AC:

10911

AN:

152034

Hom.:

553

Cov.:

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

GnomAD2 exomes

AF:

0.0743

AC:

18640

AN:

251006

AF XY:

0.0745

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 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

African (AFR)

AF:

0.0154

AC:

514

AN:

33478

American (AMR)

AF:

0.0303

AC:

1356

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

3418

AN:

26132

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.0171

AC:

1477

AN:

86258

European-Finnish (FIN)

AF:

0.131

AC:

6981

AN:

53368

Middle Eastern (MID)

AF:

0.0151

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.115

AC:

127679

AN:

1111894

Other (OTH)

AF:

0.0877

AC:

5295

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

7780

15559

23339

31118

38898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4540

9080

13620

18160

22700

<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:

0.0717

AC:

10914

AN:

152152

Hom.:

553

Cov.:

AF XY:

0.0707

AC XY:

5259

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0203

AC:

844

AN:

41550

American (AMR)

AF:

0.0370

AC:

565

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

452

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5180

South Asian (SAS)

AF:

0.0141

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.135

AC:

1428

AN:

10580

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.107

AC:

7285

AN:

67954

Other (OTH)

AF:

0.0478

AC:

101

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

511

1022

1534

2045

2556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0929

Hom.:

121

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0915

EpiControl

AF:

0.0970

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CCR5-related disorder

Benign:1

May 10, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Susceptibility to HIV infection

Benign:1

Dec 01, 2008

OMIM

Significance:protective

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Benign:1

Nov 22, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Resistance to hepatitis C virus

Benign:1

Dec 01, 2008

OMIM

Significance:protective

Review Status:no assertion criteria provided

Collection Method:literature only

- -

West Nile virus, susceptibility to

Other:1

Dec 01, 2008

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Multiple sclerosis modifier of disease progression

Other:1

Dec 01, 2008

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.89

Mutation Taster

=185/15

polymorphism (auto)

(source)

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over