rs1065341

Variant names:

• chr17-35871589-T-C
• rs1065341
• NM_002985.3:c.*788A>G

Variant summary

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

The NM_002985.3(CCL5):​c.*788A>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_002985.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• Publications: 16 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002985.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL5	NM_002985.3	MANE Select	c.*788A>G		3_prime_UTR	Exon 3 of 3	NP_002976.2
	CCL5	NM_001278736.2		c.*681A>G		3_prime_UTR	Exon 4 of 4	NP_001265665.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL5	ENST00000605140.6	TSL:5 MANE Select	c.*788A>G		3_prime_UTR	Exon 3 of 3	ENSP00000475057.1
	CCL5	ENST00000651122.1		c.*681A>G		3_prime_UTR	Exon 4 of 4	ENSP00000499138.1
	ENSG00000270240	ENST00000605548.2	TSL:3	n.183+2471T>C		intron	N/A

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0476 AC: 2 AN: 42

Other (OTH) AF: 0.167 AC: 1 AN: 6

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

African (AFR) AF: 0.244 AC: 10126 AN: 41508

American (AMR) AF: 0.0567 AC: 867 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 73 AN: 3468

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5178

South Asian (SAS) AF: 0.169 AC: 816 AN: 4830

European-Finnish (FIN) AF: 0.0303 AC: 322 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0528 AC: 3593 AN: 68000

Other (OTH) AF: 0.0805 AC: 170 AN: 2112

Alfa AF: 0.0691 Hom.: 2002

Bravo AF: 0.109

Asia WGS AF: 0.111 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-0.28

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: rs1065341; hg19: chr17-34198593;