chr3-46373570-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001394783.1(CCR5):c.668G>A(p.Arg223Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,613,554 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 93 hom. )

Consequence

CCR5
NM_001394783.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.179

Publications

32 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027464628).

BP6

Variant 3-46373570-G-A is Benign according to our data. Variant chr3-46373570-G-A is described in ClinVar as Benign. ClinVar VariationId is 8186.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR5	NM_001394783.1 link	c.668G>A	p.Arg223Gln	missense_variant	Exon 2 of 2	ENST00000292303.5	NP_001381712.1
CCR5AS	NR_125406.2 link	n.399-2153C>T		intron_variant	Intron 2 of 3	ENST00000451485.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR5	ENST00000292303.5 link	c.668G>A	p.Arg223Gln	missense_variant	Exon 2 of 2	1	NM_001394783.1	ENSP00000292303.4
CCR5AS	ENST00000451485.3 link	n.399-2153C>T		intron_variant	Intron 2 of 3	3	NR_125406.2

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

412

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.0514

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000956

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00492

AC:

1235

AN:

250954

AF XY:

0.00461

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00538

Gnomad EAS exome

AF:

0.0526

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.000978

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00275

AC:

4021

AN:

1461360

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

2025

AN XY:

726948

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33428

American (AMR)

AF:

0.000358

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00563

AC:

147

AN:

26108

East Asian (EAS)

AF:

0.0615

AC:

2443

AN:

39694

South Asian (SAS)

AF:

0.00262

AC:

226

AN:

86236

European-Finnish (FIN)

AF:

0.000468

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000888

AC:

987

AN:

1111682

Other (OTH)

AF:

0.00277

AC:

167

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

275

549

824

1098

1373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.00272

AC:

414

AN:

152194

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

225

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41530

American (AMR)

AF:

0.000392

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3468

East Asian (EAS)

AF:

0.0521

AC:

269

AN:

5166

South Asian (SAS)

AF:

0.00332

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000378

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000956

AC:

AN:

68008

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00255

Hom.:

Bravo

AF:

0.00326

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.00502

AC:

610

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00136

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CCR5 POLYMORPHISM, ORIENTAL 2

Benign:1

Jul 01, 1997

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.0

.;T

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L

PhyloP100

0.18

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.073

Sift

Benign

0.064

T;T

Sift4G

Benign

0.15

T;T

Vest4

0.044

ClinPred

0.031

GERP RS

4.8

Varity_R

0.37

gMVP

0.37

Mutation Taster

=99/1

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over