rs4987053

Positions:

• chr3-46265209-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_178329.3(CCR3):​c.51T>C​(p.Tyr17Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0804 in 1,613,712 control chromosomes in the GnomAD database, including 6,408 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 0.091 (731 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5677 hom.)
• Consequence: CCR3 NM_178329.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=0.235 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR3	NM_178329.3	c.51T>C	p.Tyr17Tyr	synonymous_variant	2/2	ENST00000395940.3	NP_847899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR3	ENST00000395940.3	c.51T>C	p.Tyr17Tyr	synonymous_variant	2/2	1	NM_178329.3	ENSP00000379271.2

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13779 AN: 152054 Hom.: 729 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0598

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.0364

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.0944

GnomAD3 exomes AF: 0.0919 AC: 23037 AN: 250582 Hom.: 1361 AF XY: 0.0980 AC XY: 13268 AN XY: 135452

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.0498

Gnomad ASJ exome AF: 0.0760

Gnomad EAS exome AF: 0.0431

Gnomad SAS exome AF: 0.195

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.0734

Gnomad OTH exome AF: 0.0852

GnomAD4 exome AF: 0.0794 AC: 115993 AN: 1461540 Hom.: 5677 Cov.: 33 AF XY: 0.0836 AC XY: 60804 AN XY: 727078

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.0514

Gnomad4 ASJ exome AF: 0.0766

Gnomad4 EAS exome AF: 0.0392

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.0683

Gnomad4 OTH exome AF: 0.0853

GnomAD4 genome AF: 0.0907 AC: 13796 AN: 152172 Hom.: 731 Cov.: 32 AF XY: 0.0949 AC XY: 7056 AN XY: 74382

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0596

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.0365

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.0703

Gnomad4 OTH AF: 0.0930

Alfa AF: 0.0726 Hom.: 612

Bravo AF: 0.0835

Asia WGS AF: 0.104 AC: 360 AN: 3478

EpiCase AF: 0.0717

EpiControl AF: 0.0705

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.73
DANN	Benign	0.16

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: rs4987053; hg19: chr3-46306700;