3-46254286-A-G

Variant names:

• chr3-46254286-A-G
• rs6441948
• NM_178329.3:c.-11-10862A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178329.3(CCR3):​c.-11-10862A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,970 control chromosomes in the GnomAD database, including 27,958 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 0.60 (27958 hom., cov: 31)
• Consequence: CCR3 NM_178329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR3	NM_178329.3	MANE Select	c.-11-10862A>G		intron	N/A	NP_847899.1
	CCR3	NM_178328.1		c.-17-10101A>G		intron	N/A	NP_847898.1
	CCR3	NM_001164680.2		c.-17-10101A>G		intron	N/A	NP_001158152.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR3	ENST00000395940.3	TSL:1 MANE Select	c.-11-10862A>G		intron	N/A	ENSP00000379271.2
	CCR3	ENST00000545097.1	TSL:1	c.-17-10101A>G		intron	N/A	ENSP00000441600.1
	CCR3	ENST00000452454.1	TSL:1	c.-80-10101A>G		intron	N/A	ENSP00000389336.1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91215 AN: 151852 Hom.: 27922 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.631

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.601 AC: 91296 AN: 151970 Hom.: 27958 Cov.: 31 AF XY: 0.609 AC XY: 45235 AN XY: 74268

African (AFR) AF: 0.622 AC: 25766 AN: 41428

American (AMR) AF: 0.668 AC: 10192 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2084 AN: 3470

East Asian (EAS) AF: 0.906 AC: 4684 AN: 5172

South Asian (SAS) AF: 0.763 AC: 3679 AN: 4820

European-Finnish (FIN) AF: 0.547 AC: 5779 AN: 10556

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37023 AN: 67948

Other (OTH) AF: 0.634 AC: 1340 AN: 2112

Alfa AF: 0.576 Hom.: 70951

Bravo AF: 0.609

Asia WGS AF: 0.794 AC: 2760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.69
PhyloP100		-0.43
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: rs6441948; hg19: chr3-46295777;