rs3181080

chr3-46208438-A-T

Variant summary

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

The ENST00000357422.2(CCR3):c.-284-2253A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 128,458 control chromosomes in the GnomAD database, including 589 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 0.081 (589 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCR3 ENST00000357422.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

Genes affected

CCR3 (HGNC:1604): (C-C motif chemokine receptor 3) The protein encoded by this gene is a receptor for C-C type chemokines. It belongs to family 1 of the G protein-coupled receptors. This receptor binds and responds to a variety of chemokines, including eotaxin (CCL11), eotaxin-3 (CCL26), MCP-3 (CCL7), MCP-4 (CCL13), and RANTES (CCL5). It is highly expressed in eosinophils and basophils, and is also detected in TH1 and TH2 cells, as well as in airway epithelial cells. This receptor may contribute to the accumulation and activation of eosinophils and other inflammatory cells in the allergic airway. It is also known to be an entry co-receptor for HIV-1. This gene and seven other chemokine receptor genes form a chemokine receptor gene cluster on the chromosomal region 3p21. Alternatively spliced transcript variants have been described. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR3	ENST00000357422.2	c.-284-2253A>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.0816 AC: 10467 AN: 128342 Hom.: 590 Cov.: 32

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.0682

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0561

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0936

Gnomad OTH AF: 0.0789

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0814 AC: 10457 AN: 128458 Hom.: 589 Cov.: 32 AF XY: 0.0896 AC XY: 5574 AN XY: 62234

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.0680

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0560

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.0935

Gnomad4 OTH AF: 0.0785

Alfa AF: 0.0732 Hom.: 69

Bravo AF: 0.0550

Asia WGS AF: 0.132 AC: 460 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	14
Dann	Benign	0.77

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: rs3181080; hg19: chr3-46249929;