rs4987125

Variant names:

• chr3-46265220-G-A
• rs4987125
• NM_178329.3:c.62G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_178329.3(CCR3):​c.62G>A​(p.Gly21Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: CCR3 NM_178329.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1650689).

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.62G>A	p.Gly21Asp	missense	Exon 2 of 2	NP_847899.1	P51677-1
	CCR3	NM_178328.1		c.125G>A	p.Gly42Asp	missense	Exon 3 of 3	NP_847898.1	P51677-2
	CCR3	NM_001164680.2		c.116G>A	p.Gly39Asp	missense	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.62G>A	p.Gly21Asp	missense	Exon 2 of 2	ENSP00000379271.2	P51677-1
	CCR3	ENST00000545097.1	TSL:1	c.125G>A	p.Gly42Asp	missense	Exon 3 of 3	ENSP00000441600.1	P51677-2
	CCR3	ENST00000452454.1	TSL:1	c.62G>A	p.Gly21Asp	missense	Exon 3 of 3	ENSP00000389336.1	Q8TDP5

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250834 AF XY: 0.0000369

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461772 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 727182

African (AFR) AF: 0.000418 AC: 14 AN: 33476

American (AMR) AF: 0.0000894 AC: 4 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111950

Other (OTH) AF: 0.0000662 AC: 4 AN: 60394

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74420

African (AFR) AF: 0.000650 AC: 27 AN: 41540

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000101 Hom.: 0

Bravo AF: 0.000249

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000659 AC: 8

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	1.4
DANN	Benign	0.96
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.14
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.27
Sift	Uncertain	0.012	D
Sift4G	Benign	0.33	T
Polyphen		0.56	P
Vest4		0.12
MVP		0.78
MPC		0.10
ClinPred		0.014	T
GERP RS		3.8
PromoterAI		-0.024	Neutral
Varity_R		0.073
gMVP		0.30
Mutation Taster		=89/11	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: rs4987125; hg19: chr3-46306711;