rs1800825

Positions:

• chr17-35880482-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000605509.2(CCL5):​c.-17-160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 606,016 control chromosomes in the GnomAD database, including 279 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 0.022 (81 hom., cov: 32)
  • Exomes 𝑓: 0.024 (198 hom.)
• Consequence: CCL5 ENST00000605509.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105371745	XR_007065724.1	n.148-3900A>G		intron_variant
LOC105371745	XR_934699.2	n.148-3900A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL5	ENST00000605509.2	c.-17-160T>C		intron_variant		3		ENSP00000474141.2
ENSG00000270240	ENST00000605548.1	n.153-3900A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3395 AN: 152224 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.00536

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0661

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.00819

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0286

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.0238 AC: 10802 AN: 453674 Hom.: 198 Cov.: 4 AF XY: 0.0234 AC XY: 5581 AN XY: 238306

Gnomad4 AFR exome AF: 0.00564

Gnomad4 AMR exome AF: 0.0829

Gnomad4 ASJ exome AF: 0.00418

Gnomad4 EAS exome AF: 0.0000643

Gnomad4 SAS exome AF: 0.0182

Gnomad4 FIN exome AF: 0.0111

Gnomad4 NFE exome AF: 0.0268

Gnomad4 OTH exome AF: 0.0227

GnomAD4 genome AF: 0.0223 AC: 3393 AN: 152342 Hom.: 81 Cov.: 32 AF XY: 0.0223 AC XY: 1660 AN XY: 74504

Gnomad4 AFR AF: 0.00534

Gnomad4 AMR AF: 0.0661

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.00819

Gnomad4 NFE AF: 0.0286

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0327 Hom.: 43

Bravo AF: 0.0245

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.88

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: rs1800825; hg19: chr17-34207486;