rs2107538

Variant names:

• chr17-35880776-C-T
• rs2107538
• ENST00000605509.2:c.-65G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 254 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:58767):

LOC105371745 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000605509.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL5	ENST00000605509.2	TSL:3	c.-65G>A		5_prime_UTR	Exon 1 of 4	ENSP00000474141.2	P13501
	ENSG00000270240	ENST00000605548.2	TSL:3	n.184-3606C>T		intron	N/A
	ENSG00000270240	ENST00000788495.1		n.257+702C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40212 AN: 151968 Hom.: 6290 Cov.: 32

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.: 0 AF XY: 0.192 AC XY: 1129 AN XY: 5884

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: 37 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: 18 AN: 200

Middle Eastern (MID) AF: 0.200 AC: 6 AN: 30

European-Non Finnish (NFE) AF: 0.155 AC: 1043 AN: 6728

Other (OTH) AF: 0.174 AC: 98 AN: 562

GnomAD4 genome AF: 0.265 AC: 40309 AN: 152086 Hom.: 6325 Cov.: 32 AF XY: 0.265 AC XY: 19740 AN XY: 74356

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: 58 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12221 AN: 67996

Other (OTH) AF: 0.232 AC: 488 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.79
PhyloP100		-0.43
PromoterAI		0.26	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2107538;

hg19: chr17-34207780;