dbSNP rs2107538: CCL5:c.-65G>A (chr17-35880776-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000605509.2(CCL5):c.-65G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 163,666 control chromosomes in the GnomAD database, including 6,602 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 0.27 ( 6325 hom., cov: 32)

Exomes 𝑓: 0.19 ( 277 hom. )

Consequence

CCL5
ENST00000605509.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.426

Publications

252 publications found

Variant links:

Genes affected

CCL5 (HGNC:10632): (C-C motif chemokine ligand 5) This gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CC subfamily, functions as a chemoattractant for blood monocytes, memory T helper cells and eosinophils. It causes the release of histamine from basophils and activates eosinophils. This cytokine is one of the major HIV-suppressive factors produced by CD8+ cells. It functions as one of the natural ligands for the chemokine receptor chemokine (C-C motif) receptor 5 (CCR5), and it suppresses in vitro replication of the R5 strains of HIV-1, which use CCR5 as a coreceptor. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Jul 2013]

CCL5 links:

ENSG00000270240 (HGNC:):

ENSG00000270240 links:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105371745	XR_007065724.1 link	n.148-3606C>T		intron_variant	Intron 1 of 4
LOC105371745	XR_934699.2 link	n.148-3606C>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
CCL5	ENST00000605509.2 link	c.-65G>A	5_prime_UTR_variant	Exon 1 of 4	3	ENSP00000474141.2	P13501
ENSG00000270240	ENST00000605548.2 link	n.184-3606C>T	intron_variant	Intron 1 of 4	3
ENSG00000270240	ENST00000788495.1 link	n.257+702C>T	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40212

AN:

151968

Hom.:

6290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.189

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.231

GnomAD4 exome

AF:

0.191

AC:

2210

AN:

11580

Hom.:

277

Cov.:

AF XY:

0.192

AC XY:

1129

AN XY:

5884

show subpopulations

African (AFR)

AF:

0.368

AC:

117

AN:

318

American (AMR)

AF:

0.225

AC:

449

AN:

1996

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

AN:

190

East Asian (EAS)

AF:

0.328

AC:

245

AN:

746

South Asian (SAS)

AF:

0.243

AC:

197

AN:

810

European-Finnish (FIN)

AF:

0.0900

AC:

AN:

200

Middle Eastern (MID)

AF:

0.200

AC:

AN:

European-Non Finnish (NFE)

AF:

0.155

AC:

1043

AN:

6728

Other (OTH)

AF:

0.174

AC:

AN:

562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

170

256

341

426

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:

0.265

AC:

40309

AN:

152086

Hom.:

6325

Cov.:

AF XY:

0.265

AC XY:

19740

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.434

AC:

17970

AN:

41452

American (AMR)

AF:

0.235

AC:

3597

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

656

AN:

3468

East Asian (EAS)

AF:

0.342

AC:

1773

AN:

5180

South Asian (SAS)

AF:

0.303

AC:

1457

AN:

4814

European-Finnish (FIN)

AF:

0.178

AC:

1883

AN:

10582

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12221

AN:

67996

Other (OTH)

AF:

0.232

AC:

488

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1407

2815

4222

5630

7037

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.273

Hom.:

2898

Bravo

AF:

0.276

Asia WGS

AF:

0.308

AC:

1070

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.7

(source)

DANN

Benign

0.79

PhyloP100

-0.43

PromoterAI

0.26

Neutral

(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

Computational scores

Splicing

Publications

Other links and lift over