ENST00000357422.2:c.-284-2253A>T

Variant names:

• chr3-46208438-A-T
• rs3181080
• ENST00000357422.2:c.-284-2253A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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]

CCR1 (HGNC:1602): (C-C motif chemokine receptor 1) This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. The ligands of this receptor include macrophage inflammatory protein 1 alpha (MIP-1 alpha), regulated on activation normal T expressed and secreted protein (RANTES), monocyte chemoattractant protein 3 (MCP-3), and myeloid progenitor inhibitory factor-1 (MPIF-1). Chemokines and their receptors mediated signal transduction are critical for the recruitment of effector immune cells to the site of inflammation. Knockout studies of the mouse homolog suggested the roles of this gene in host protection from inflammatory response, and susceptibility to virus and parasite. This gene and other chemokine receptor genes, including CCR2, CCRL2, CCR3, CCR5 and CCXCR1, are found to form a gene cluster on chromosome 3p. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCR1	NM_001295.3	c.-168T>A		upstream_gene_variant		ENST00000296140.4	NP_001286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR3	ENST00000357422.2	c.-284-2253A>T		intron_variant	Intron 1 of 3	2		ENSP00000350003.2
CCR1	ENST00000296140.4	c.-168T>A		upstream_gene_variant		1	NM_001295.3	ENSP00000296140.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0146 AC: 527 AN: 36128

American (AMR) AF: 0.0680 AC: 776 AN: 11414

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 379 AN: 3032

East Asian (EAS) AF: 0.0560 AC: 203 AN: 3626

South Asian (SAS) AF: 0.336 AC: 1323 AN: 3938

European-Finnish (FIN) AF: 0.162 AC: 1421 AN: 8788

Middle Eastern (MID) AF: 0.146 AC: 38 AN: 260

European-Non Finnish (NFE) AF: 0.0935 AC: 5492 AN: 58730

Other (OTH) AF: 0.0785 AC: 133 AN: 1694

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
PhyloP100		1.4
PromoterAI		0.17	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs3181080; hg19: chr3-46249929;