rs5742906

Positions:

• chr3-46265274-C-G
• chr3-46265274-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_178329.3(CCR3):​c.116C>G​(p.Pro39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P39L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCR3 NM_178329.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.776

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR3	NM_178329.3	c.116C>G	p.Pro39Arg	missense_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.116C>G	p.Pro39Arg	missense_variant	2/2	1	NM_178329.3	ENSP00000379271	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.00094	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;.;T;.;T
Eigen	Benign	0.085
Eigen_PC	Benign	-0.053
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.96	.;D;.;T;D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.78	D;D;D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.5	M;.;M;.;M
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-7.0	D;D;D;D;D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Uncertain	0.030	D;D;D;T;D
Polyphen		1.0	D;.;D;D;D
Vest4		0.40
MutPred		0.79		Gain of methylation at P39 (P = 0.0121);.;Gain of methylation at P39 (P = 0.0121);Gain of methylation at P39 (P = 0.0121);Gain of methylation at P39 (P = 0.0121);
MVP		0.66
MPC		0.37
ClinPred		0.76	D
GERP RS		5.2
Varity_R		0.58
gMVP		0.53

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: rs5742906; hg19: chr3-46306765;