chr3-46261693-A-G

Variant names:

• chr3-46261693-A-G
• rs3091309
• NM_178329.3:c.-11-3455A>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.-11-3455A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,246 control chromosomes in the GnomAD database, including 58,541 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 0.87 (58541 hom., cov: 32)
• Consequence: CCR3 NM_178329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.954
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR3	NM_178329.3	c.-11-3455A>G		intron_variant	Intron 1 of 1	ENST00000395940.3	NP_847899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR3	ENST00000395940.3	c.-11-3455A>G		intron_variant	Intron 1 of 1	1	NM_178329.3	ENSP00000379271.2

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132836 AN: 152128 Hom.: 58472 Cov.: 32

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.882

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

GnomAD4 genome AF: 0.873 AC: 132966 AN: 152246 Hom.: 58541 Cov.: 32 AF XY: 0.877 AC XY: 65285 AN XY: 74450

African (AFR) AF: 0.966 AC: 40143 AN: 41572

American (AMR) AF: 0.896 AC: 13703 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3091 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5173 AN: 5176

South Asian (SAS) AF: 0.956 AC: 4616 AN: 4826

European-Finnish (FIN) AF: 0.819 AC: 8684 AN: 10602

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54653 AN: 67984

Other (OTH) AF: 0.883 AC: 1868 AN: 2116

Alfa AF: 0.854 Hom.: 37265

Bravo AF: 0.883

Asia WGS AF: 0.980 AC: 3405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.44
PhyloP100		-0.95
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: rs3091309; hg19: chr3-46303184;