rs4987053

Variant names:

• chr3-46265209-T-C
• rs4987053
• NM_178329.3:c.51T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 33 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178329.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR3	NM_178329.3	MANE Select	c.51T>C	p.Tyr17Tyr	synonymous	Exon 2 of 2	NP_847899.1	P51677-1
	CCR3	NM_178328.1		c.114T>C	p.Tyr38Tyr	synonymous	Exon 3 of 3	NP_847898.1	P51677-2
	CCR3	NM_001164680.2		c.105T>C	p.Tyr35Tyr	synonymous	Exon 3 of 3	NP_001158152.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR3	ENST00000395940.3	TSL:1 MANE Select	c.51T>C	p.Tyr17Tyr	synonymous	Exon 2 of 2	ENSP00000379271.2	P51677-1
	CCR3	ENST00000545097.1	TSL:1	c.114T>C	p.Tyr38Tyr	synonymous	Exon 3 of 3	ENSP00000441600.1	P51677-2
	CCR3	ENST00000452454.1	TSL:1	c.51T>C	p.Tyr17Tyr	synonymous	Exon 3 of 3	ENSP00000389336.1	Q8TDP5

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

GnomAD2 exomes AF: 0.0919 AC: 23037 AN: 250582 AF XY: 0.0980

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 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

African (AFR) AF: 0.126 AC: 4233 AN: 33474

American (AMR) AF: 0.0514 AC: 2298 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 2001 AN: 26124

East Asian (EAS) AF: 0.0392 AC: 1556 AN: 39672

South Asian (SAS) AF: 0.195 AC: 16812 AN: 86246

European-Finnish (FIN) AF: 0.134 AC: 7159 AN: 53414

Middle Eastern (MID) AF: 0.140 AC: 805 AN: 5758

European-Non Finnish (NFE) AF: 0.0683 AC: 75975 AN: 1111742

Other (OTH) AF: 0.0853 AC: 5154 AN: 60390

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

African (AFR) AF: 0.119 AC: 4930 AN: 41514

American (AMR) AF: 0.0596 AC: 911 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3470

East Asian (EAS) AF: 0.0365 AC: 189 AN: 5184

South Asian (SAS) AF: 0.190 AC: 914 AN: 4818

European-Finnish (FIN) AF: 0.138 AC: 1463 AN: 10576

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0703 AC: 4783 AN: 68012

Other (OTH) AF: 0.0930 AC: 196 AN: 2108

Alfa AF: 0.0738 Hom.: 838

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.73
DANN	Benign	0.16
PhyloP100		0.23
PromoterAI		0.031	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: rs4987053; hg19: chr3-46306700;