NM_001278736.2:c.76+231T>C

Variant names:

• chr17-35879999-A-G
• rs2280789
• NM_002985.3:c.76+231T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PP5 BP4 BA1

The NM_001278736.2(CCL5):​c.76+231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,178 control chromosomes in the GnomAD database, including 2,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: 𝑓 0.16 (2242 hom., cov: 32)
• Consequence: CCL5 NM_001278736.2 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.569
• Publications: 74 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 -8 ACMG points.

• PP5: Variant 17-35879999-A-G is Pathogenic according to our data. Variant chr17-35879999-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 12740.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86). . Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278736.2. 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
	CCL5	NM_002985.3	MANE Select	c.76+231T>C		intron	N/A	NP_002976.2
	CCL5	NM_001278736.2		c.76+231T>C		intron	N/A	NP_001265665.1	A0A494C1Q1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL5	ENST00000605140.6	TSL:5 MANE Select	c.76+231T>C		intron	N/A	ENSP00000475057.1	P13501
	CCL5	ENST00000651122.1		c.76+231T>C		intron	N/A	ENSP00000499138.1	A0A494C1Q1
	CCL5	ENST00000605509.2	TSL:3	c.76+231T>C		intron	N/A	ENSP00000474141.2	P13501

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24682 AN: 152060 Hom.: 2229 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.162 AC: 24726 AN: 152178 Hom.: 2242 Cov.: 32 AF XY: 0.163 AC XY: 12153 AN XY: 74398

African (AFR) AF: 0.199 AC: 8262 AN: 41502

American (AMR) AF: 0.182 AC: 2780 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1711 AN: 5178

South Asian (SAS) AF: 0.132 AC: 637 AN: 4818

European-Finnish (FIN) AF: 0.148 AC: 1567 AN: 10586

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8645 AN: 68008

Other (OTH) AF: 0.158 AC: 333 AN: 2110

Alfa AF: 0.158 Hom.: 551

Bravo AF: 0.171

Asia WGS AF: 0.198 AC: 690 AN: 3478

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Human immunodeficiency virus type 1, rapid disease progression with infection by (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.1
DANN	Benign	0.79
PhyloP100		0.57
PromoterAI		-0.015	Neutral

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: rs2280789; hg19: chr17-34207003;