rs4796120

chr17-35873887-A-G

Variant summary

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

The NM_001278736.2(CCL5):c.271-1423T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 152,218 control chromosomes in the GnomAD database, including 872 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 0.094 (872 hom., cov: 32)
• Consequence: CCL5 NM_001278736.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL5	NM_002985.3	c.189-1423T>C		intron_variant		ENST00000605140.6
LOC105371745	XR_007065724.1	n.147+4769A>G		intron_variant, non_coding_transcript_variant
CCL5	NM_001278736.2	c.271-1423T>C		intron_variant
LOC105371745	XR_934699.2	n.147+4769A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL5	ENST00000605140.6	c.189-1423T>C		intron_variant		5	NM_002985.3	P1
	ENST00000605548.1	n.152+4769A>G		intron_variant, non_coding_transcript_variant		3
CCL5	ENST00000605509.2	c.189-1423T>C		intron_variant		3		P1
CCL5	ENST00000651122.1	c.271-1423T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14339 AN: 152100 Hom.: 868 Cov.: 32

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0943 AC: 14359 AN: 152218 Hom.: 872 Cov.: 32 AF XY: 0.0963 AC XY: 7165 AN XY: 74414

Gnomad4 AFR AF: 0.0353

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.104

Alfa AF: 0.108 Hom.: 719

Bravo AF: 0.0982

Asia WGS AF: 0.142 AC: 495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.19
Dann	Benign	0.71

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: rs4796120; hg19: chr17-34200891;