17-35879999-A-G

Position:

• chr17-35879999-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP5 BP4 BA1

The NM_001278736.2(CCL5):​c.76+231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,178 control chromosomes in the GnomAD database, including 2,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: 𝑓 0.16 (2242 hom., cov: 32)
• Consequence: CCL5 NM_001278736.2 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.569

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PP5: Variant 17-35879999-A-G is Pathogenic according to our data. Variant chr17-35879999-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 12740.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86). . Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL5	NM_002985.3	c.76+231T>C		intron_variant		ENST00000605140.6
LOC105371745	XR_007065724.1	n.148-4383A>G		intron_variant, non_coding_transcript_variant
CCL5	NM_001278736.2	c.76+231T>C		intron_variant
LOC105371745	XR_934699.2	n.148-4383A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL5	ENST00000605140.6	c.76+231T>C		intron_variant		5	NM_002985.3	P1
	ENST00000605548.1	n.153-4383A>G		intron_variant, non_coding_transcript_variant		3
CCL5	ENST00000605509.2	c.76+231T>C		intron_variant		3		P1
CCL5	ENST00000651122.1	c.76+231T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24682 AN: 152060 Hom.: 2229 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.156

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24726 AN: 152178 Hom.: 2242 Cov.: 32 AF XY: 0.163 AC XY: 12153 AN XY: 74398

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.158

Alfa AF: 0.139 Hom.: 286

Bravo AF: 0.171

Asia WGS AF: 0.198 AC: 690 AN: 3478

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

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

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 23, 2002

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.1
DANN	Benign	0.79

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

LitVar

Other links and lift over

dbSNP: rs2280789; hg19: chr17-34207003;