Genetic Variant CCR5:c.*1018G>T (chr3-46374979-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394783.1(CCR5):c.*1018G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 167,170 control chromosomes in the GnomAD database, including 8,477 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 0.30 ( 7756 hom., cov: 30)

Exomes 𝑓: 0.31 ( 721 hom. )

Consequence

CCR5
NM_001394783.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.367

Publications

13 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 (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR5	NM_001394783.1 link	c.*1018G>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000292303.5	NP_001381712.1
CCR5AS	NR_125406.2 link	n.399-3562C>A		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.*1018G>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_001394783.1	ENSP00000292303.4
CCR5AS	ENST00000451485.3 link	n.399-3562C>A		intron_variant	Intron 2 of 3	3	NR_125406.2

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45459

AN:

151658

Hom.:

7756

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.335

Gnomad AMR

AF:

0.376

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.554

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.346

GnomAD4 exome

AF:

0.306

AC:

4709

AN:

15392

Hom.:

721

Cov.:

AF XY:

0.303

AC XY:

2235

AN XY:

7376

show subpopulations

African (AFR)

AF:

0.0833

AC:

AN:

American (AMR)

AF:

0.333

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.305

AC:

4584

AN:

15020

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.345

AC:

AN:

232

Other (OTH)

AF:

0.308

AC:

AN:

104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

241

482

722

963

1204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.300

AC:

45464

AN:

151778

Hom.:

7756

Cov.:

AF XY:

0.303

AC XY:

22478

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.126

AC:

5216

AN:

41448

American (AMR)

AF:

0.376

AC:

5738

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

1328

AN:

3470

East Asian (EAS)

AF:

0.553

AC:

2833

AN:

5122

South Asian (SAS)

AF:

0.411

AC:

1976

AN:

4804

European-Finnish (FIN)

AF:

0.306

AC:

3211

AN:

10500

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.354

AC:

24008

AN:

67870

Other (OTH)

AF:

0.344

AC:

725

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1497

2994

4492

5989

7486

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:

0.271

Hom.:

1869

Bravo

AF:

0.297

Asia WGS

AF:

0.413

AC:

1437

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.9

(source)

DANN

Benign

0.62

PhyloP100

0.37

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