rs2107538

Positions:

• chr17-35880776-C-T

Variant summary

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

The ENST00000605548.1(ENSG00000270240):​n.153-3606C>T 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 0.26 in 163,666 control chromosomes in the GnomAD database, including 6,602 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 0.27 (6325 hom., cov: 32)
  • Exomes 𝑓: 0.19 (277 hom.)
• Consequence: ENST00000605548.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105371745	XR_007065724.1	n.148-3606C>T		intron_variant, non_coding_transcript_variant
LOC105371745	XR_934699.2	n.148-3606C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000605548.1	n.153-3606C>T		intron_variant, non_coding_transcript_variant		3
CCL5	ENST00000605509.2	c.-65G>A		5_prime_UTR_variant	1/4	3		ENSP00000474141	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40212 AN: 151968 Hom.: 6290 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.191 AC: 2210 AN: 11580 Hom.: 277 Cov.: 0 AF XY: 0.192 AC XY: 1129 AN XY: 5884

Gnomad4 AFR exome AF: 0.368

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.328

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.0900

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.265 AC: 40309 AN: 152086 Hom.: 6325 Cov.: 32 AF XY: 0.265 AC XY: 19740 AN XY: 74356

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.232

Alfa AF: 0.226 Hom.: 821

Bravo AF: 0.276

Asia WGS AF: 0.308 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2107538; hg19: chr17-34207780;