Genetic Variant NM_001278736.2:c.*681A>G (chr17-35871589-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001278736.2(CCL5):c.*681A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,290 control chromosomes in the GnomAD database, including 1,425 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 0.11 ( 1425 hom., cov: 31)

Exomes 𝑓: 0.039 ( 0 hom. )

Consequence

CCL5
NM_001278736.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.277

Publications

16 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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CCL5	NM_001278736.2 link	c.*681A>G	3_prime_UTR_variant	Exon 4 of 4	ENST00000651122.1	NP_001265665.1	A0A494C1Q1
CCL5	NM_002985.3 link	c.*788A>G	3_prime_UTR_variant	Exon 3 of 3		NP_002976.2	P13501D0EI67
LOC105371745	XR_007065724.1 link	n.147+2471T>C	intron_variant	Intron 1 of 4
LOC105371745	XR_934699.2 link	n.147+2471T>C	intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL5	ENST00000651122.1 link	c.*681A>G		3_prime_UTR_variant	Exon 4 of 4		NM_001278736.2	ENSP00000499138.1		A0A494C1Q1
CCL5	ENST00000605140.6 link	c.*788A>G		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000475057.1		P13501

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

16031

AN:

152096

Hom.:

1405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.0573

Gnomad AMR

AF:

0.0568

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.0121

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.0303

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0528

Gnomad OTH

AF:

0.0813

GnomAD4 exome

AF:

0.0395

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0600

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0476

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.608

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.106

AC:

16088

AN:

152214

Hom.:

1425

Cov.:

AF XY:

0.105

AC XY:

7844

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.244

AC:

10126

AN:

41508

American (AMR)

AF:

0.0567

AC:

867

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

AN:

3468

East Asian (EAS)

AF:

0.0122

AC:

AN:

5178

South Asian (SAS)

AF:

0.169

AC:

816

AN:

4830

European-Finnish (FIN)

AF:

0.0303

AC:

322

AN:

10616

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0528

AC:

3593

AN:

68000

Other (OTH)

AF:

0.0805

AC:

170

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

665

1330

1994

2659

3324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.0691

Hom.:

2002

Bravo

AF:

0.109

Asia WGS

AF:

0.111

AC:

384

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.4

(source)

DANN

Benign

0.55

PhyloP100

-0.28

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over