rs2280788

Variant names:

• chr17-35880401-G-C
• rs2280788
• ENST00000605509.2:c.-17-79C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000605509.2(CCL5):​c.-17-79C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 969,316 control chromosomes in the GnomAD database, including 620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (67 hom., cov: 32)
  • Exomes 𝑓: 0.028 (553 hom.)
• Consequence: CCL5 ENST00000605509.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter P:1 B:1
• Conservation: PhyloP100: 0.279
• Publications: 173 publications found

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]

ENSG00000270240 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-35880401-G-C is Benign according to our data. Variant chr17-35880401-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 12739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) 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
LOC105371745	XR_007065724.1	n.148-3981G>C		intron_variant	Intron 1 of 4
LOC105371745	XR_934699.2	n.148-3981G>C		intron_variant	Intron 1 of 4
CCL5	NM_001278736.2	c.-96C>G		upstream_gene_variant		ENST00000651122.1	NP_001265665.1
CCL5	NM_002985.3	c.-96C>G		upstream_gene_variant			NP_002976.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL5	ENST00000651122.1	c.-96C>G		upstream_gene_variant			NM_001278736.2	ENSP00000499138.1
CCL5	ENST00000605140.6	c.-96C>G		upstream_gene_variant		5		ENSP00000475057.1

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3240 AN: 152216 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.00492

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0357

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0250

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.0276 AC: 22574 AN: 816982 Hom.: 553 Cov.: 11 AF XY: 0.0269 AC XY: 11344 AN XY: 421682

African (AFR) AF: 0.00527 AC: 108 AN: 20490

American (AMR) AF: 0.0111 AC: 378 AN: 33924

Ashkenazi Jewish (ASJ) AF: 0.0166 AC: 350 AN: 21038

East Asian (EAS) AF: 0.135 AC: 4478 AN: 33050

South Asian (SAS) AF: 0.0106 AC: 711 AN: 66972

European-Finnish (FIN) AF: 0.0315 AC: 1524 AN: 48388

Middle Eastern (MID) AF: 0.00396 AC: 14 AN: 3534

European-Non Finnish (NFE) AF: 0.0254 AC: 13989 AN: 550998

Other (OTH) AF: 0.0265 AC: 1022 AN: 38588

GnomAD4 genome AF: 0.0212 AC: 3237 AN: 152334 Hom.: 67 Cov.: 32 AF XY: 0.0224 AC XY: 1669 AN XY: 74484

African (AFR) AF: 0.00491 AC: 204 AN: 41582

American (AMR) AF: 0.0120 AC: 183 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 46 AN: 3472

East Asian (EAS) AF: 0.113 AC: 584 AN: 5172

South Asian (SAS) AF: 0.0145 AC: 70 AN: 4832

European-Finnish (FIN) AF: 0.0357 AC: 379 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0250 AC: 1701 AN: 68034

Other (OTH) AF: 0.0175 AC: 37 AN: 2114

Alfa AF: 0.0209 Hom.: 5

Bravo AF: 0.0201

Asia WGS AF: 0.0440 AC: 152 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Human immunodeficiency virus type 1, delayed disease progression with infection by Pathogenic:1

Mar 01, 2003

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

CCL5-related condition Benign:1

Jan 22, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.49
PhyloP100		0.28
PromoterAI		0.18	Neutral

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

Other links and lift over

dbSNP: rs2280788; hg19: chr17-34207405;