rs2280788

Positions:

• chr17-35880401-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP5 BP4 BA1

The ENST00000605548.1(ENSG00000270240):​n.153-3981G>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 969,316 control chromosomes in the GnomAD database, including 620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.021 (67 hom., cov: 32)
  • Exomes 𝑓: 0.028 (553 hom.)
• Consequence: ENST00000605548.1 intron, non_coding_transcript
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.279

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PP5: Variant 17-35880401-G-C is Pathogenic according to our data. Variant chr17-35880401-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 12739.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85). . Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105371745	XR_007065724.1	n.148-3981G>C		intron_variant, non_coding_transcript_variant
LOC105371745	XR_934699.2	n.148-3981G>C		intron_variant, non_coding_transcript_variant
CCL5	NM_002985.3			upstream_gene_variant		ENST00000605140.6	NP_002976.2
CCL5	NM_001278736.2			upstream_gene_variant			NP_001265665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000605548.1	n.153-3981G>C		intron_variant, non_coding_transcript_variant		3
CCL5	ENST00000605509.2	c.-17-79C>G		intron_variant		3		ENSP00000474141	P1
CCL5	ENST00000605140.6			upstream_gene_variant		5	NM_002985.3	ENSP00000475057	P1
CCL5	ENST00000651122.1			upstream_gene_variant				ENSP00000499138

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3240 AN: 152216 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.00492

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0357

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0250

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.0276 AC: 22574 AN: 816982 Hom.: 553 Cov.: 11 AF XY: 0.0269 AC XY: 11344 AN XY: 421682

Gnomad4 AFR exome AF: 0.00527

Gnomad4 AMR exome AF: 0.0111

Gnomad4 ASJ exome AF: 0.0166

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.0106

Gnomad4 FIN exome AF: 0.0315

Gnomad4 NFE exome AF: 0.0254

Gnomad4 OTH exome AF: 0.0265

GnomAD4 genome AF: 0.0212 AC: 3237 AN: 152334 Hom.: 67 Cov.: 32 AF XY: 0.0224 AC XY: 1669 AN XY: 74484

Gnomad4 AFR AF: 0.00491

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.0357

Gnomad4 NFE AF: 0.0250

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0209 Hom.: 5

Bravo AF: 0.0201

Asia WGS AF: 0.0440 AC: 152 AN: 3478

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Human immunodeficiency virus type 1, delayed disease progression with infection by Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.0
DANN	Benign	0.49

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: rs2280788; hg19: chr17-34207405;