ENST00000357422.2:c.-68+1168A>G

Variant names:

• chr3-46212075-A-G
• rs17283264
• ENST00000357422.2:c.-68+1168A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000357422.2(CCR3):​c.-68+1168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 152,084 control chromosomes in the GnomAD database, including 275 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 0.053 (275 hom., cov: 31)
• Consequence: CCR3 ENST00000357422.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• Publications: 11 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR3	XM_006712960.4	c.-68+1168A>G		intron_variant	Intron 1 of 2		XP_006713023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR3	ENST00000357422.2	c.-68+1168A>G		intron_variant	Intron 2 of 3	2		ENSP00000350003.2

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8030 AN: 151966 Hom.: 275 Cov.: 31

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00664

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0788

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0528 AC: 8026 AN: 152084 Hom.: 275 Cov.: 31 AF XY: 0.0523 AC XY: 3885 AN XY: 74330

African (AFR) AF: 0.0146 AC: 604 AN: 41484

American (AMR) AF: 0.0510 AC: 779 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 189 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00644 AC: 31 AN: 4816

European-Finnish (FIN) AF: 0.0891 AC: 941 AN: 10566

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0788 AC: 5355 AN: 67986

Other (OTH) AF: 0.0426 AC: 90 AN: 2112

Alfa AF: 0.0686 Hom.: 710

Bravo AF: 0.0475

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.28
PhyloP100		-0.49
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: rs17283264; hg19: chr3-46253566;