rs9853223

Positions:

• chr3-46242602-G-A

Variant summary

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

The NM_178329.3(CCR3):​c.-12+64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,774 control chromosomes in the GnomAD database, including 14,794 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 0.44 (14794 hom., cov: 29)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: CCR3 NM_178329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR3	NM_178329.3	c.-12+64G>A		intron_variant		ENST00000395940.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR3	ENST00000395940.3	c.-12+64G>A		intron_variant		1	NM_178329.3	P1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66655 AN: 151644 Hom.: 14770 Cov.: 29

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.0833 AC: 1 AN: 12 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.440 AC: 66716 AN: 151762 Hom.: 14794 Cov.: 29 AF XY: 0.439 AC XY: 32556 AN XY: 74136

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.429

Alfa AF: 0.431 Hom.: 7715

Bravo AF: 0.441

Asia WGS AF: 0.347 AC: 1206 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	0.28
DANN	Benign	0.27

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: rs9853223; hg19: chr3-46284093;