rs1065341

Positions:

• chr17-35871589-T-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277

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 -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL5	NM_002985.3	c.*788A>G		3_prime_UTR_variant	3/3	ENST00000605140.6	NP_002976.2
LOC105371745	XR_007065724.1	n.147+2471T>C		intron_variant, non_coding_transcript_variant
CCL5	NM_001278736.2	c.*681A>G		3_prime_UTR_variant	4/4		NP_001265665.1
LOC105371745	XR_934699.2	n.147+2471T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL5	ENST00000605140.6	c.*788A>G		3_prime_UTR_variant	3/3	5	NM_002985.3	ENSP00000475057	P1
	ENST00000605548.1	n.152+2471T>C		intron_variant, non_coding_transcript_variant		3
CCL5	ENST00000651122.1	c.*681A>G		3_prime_UTR_variant	4/4			ENSP00000499138

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16031 AN: 152096 Hom.: 1405 Cov.: 31

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: 3 AN: 76 Hom.: 0 Cov.: 0 AF XY: 0.0600 AC XY: 3 AN XY: 50

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0476

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.106 AC: 16088 AN: 152214 Hom.: 1425 Cov.: 31 AF XY: 0.105 AC XY: 7844 AN XY: 74436

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.0567

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.0528

Gnomad4 OTH AF: 0.0805

Alfa AF: 0.0573 Hom.: 517

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
DANN	Benign	0.55

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: rs1065341; hg19: chr17-34198593;