3-46264639-G-T

Position:

• chr3-46264639-G-T

Variant summary

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

The NM_178329.3(CCR3):​c.-11-509G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 538,288 control chromosomes in the GnomAD database, including 24,675 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 (5969 hom., cov: 31)
  • Exomes 𝑓: 0.29 (18706 hom.)
• Consequence: CCR3 NM_178329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451

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]

CCR3 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR3	NM_178329.3	c.-11-509G>T		intron_variant		ENST00000395940.3	NP_847899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR3	ENST00000395940.3	c.-11-509G>T		intron_variant		1	NM_178329.3	ENSP00000379271.2

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40862 AN: 151582 Hom.: 5948 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.295 AC: 114020 AN: 386592 Hom.: 18706 Cov.: 0 AF XY: 0.301 AC XY: 61897 AN XY: 205716

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.344

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.588

Gnomad4 SAS exome AF: 0.405

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.251

Gnomad4 OTH exome AF: 0.292

GnomAD4 genome AF: 0.270 AC: 40916 AN: 151696 Hom.: 5969 Cov.: 31 AF XY: 0.276 AC XY: 20417 AN XY: 74102

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.296

Alfa AF: 0.259 Hom.: 1065

Bravo AF: 0.273

Asia WGS AF: 0.482 AC: 1668 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.21

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: rs3091250; hg19: chr3-46306130;