3-46265274-C-G

Variant names:

• chr3-46265274-C-G
• rs5742906
• NM_178329.3:c.116C>G

Variant summary

Our verdict is Uncertain significance. The variant received 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCR3 NM_178329.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 20 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: Uncertain_significance. The variant received 3 ACMG points.

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

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR3	NM_178329.3	MANE Select	c.116C>G	p.Pro39Arg	missense	Exon 2 of 2	NP_847899.1
	CCR3	NM_178328.1		c.179C>G	p.Pro60Arg	missense	Exon 3 of 3	NP_847898.1
	CCR3	NM_001164680.2		c.170C>G	p.Pro57Arg	missense	Exon 3 of 3	NP_001158152.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR3	ENST00000395940.3	TSL:1 MANE Select	c.116C>G	p.Pro39Arg	missense	Exon 2 of 2	ENSP00000379271.2
	CCR3	ENST00000545097.1	TSL:1	c.179C>G	p.Pro60Arg	missense	Exon 3 of 3	ENSP00000441600.1
	CCR3	ENST00000452454.1	TSL:1	c.116C>G	p.Pro39Arg	missense	Exon 3 of 3	ENSP00000389336.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.085
Eigen_PC	Benign	-0.053
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.031
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.79		Gain of methylation at P39 (P = 0.0121)
MVP		0.66
MPC		0.37
ClinPred		0.76	D
GERP RS		5.2
PromoterAI		0.012	Neutral
Varity_R		0.58
gMVP		0.53
Mutation Taster		=96/4	polymorphism

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: rs5742906; hg19: chr3-46306765;