NM_001278736.2:c.271-1423T>C

Variant names:

• chr17-35873887-A-G
• rs4796120
• NM_001278736.2:c.271-1423T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCL5	NM_001278736.2	c.271-1423T>C		intron_variant	Intron 3 of 3	ENST00000651122.1	NP_001265665.1
CCL5	NM_002985.3	c.189-1423T>C		intron_variant	Intron 2 of 2		NP_002976.2
LOC105371745	XR_007065724.1	n.147+4769A>G		intron_variant	Intron 1 of 4
LOC105371745	XR_934699.2	n.147+4769A>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL5	ENST00000651122.1	c.271-1423T>C		intron_variant	Intron 3 of 3		NM_001278736.2	ENSP00000499138.1
CCL5	ENST00000605140.6	c.189-1423T>C		intron_variant	Intron 2 of 2	5		ENSP00000475057.1

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

African (AFR) AF: 0.0353 AC: 1468 AN: 41546

American (AMR) AF: 0.151 AC: 2302 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3466

East Asian (EAS) AF: 0.219 AC: 1135 AN: 5176

South Asian (SAS) AF: 0.113 AC: 544 AN: 4824

European-Finnish (FIN) AF: 0.111 AC: 1182 AN: 10606

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6840 AN: 68004

Other (OTH) AF: 0.104 AC: 220 AN: 2116

Alfa AF: 0.106 Hom.: 1002

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
PhyloP100		-2.4

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: rs4796120; hg19: chr17-34200891;