rs13073976

Variant names:

• chr3-46245172-T-C
• rs13073976
• NM_178329.3:c.-12+2634T>C

Variant summary

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

The NM_178329.3(CCR3):​c.-12+2634T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0576 in 151,996 control chromosomes in the GnomAD database, including 386 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 0.058 (386 hom., cov: 30)
• Consequence: CCR3 NM_178329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR3	NM_178329.3	c.-12+2634T>C		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.-12+2634T>C		intron_variant	Intron 1 of 1	1	NM_178329.3	ENSP00000379271.2

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8768 AN: 151876 Hom.: 387 Cov.: 30

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0368

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0692

Gnomad OTH AF: 0.0546

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

GnomAD4 genome AF: 0.0576 AC: 8761 AN: 151996 Hom.: 386 Cov.: 30 AF XY: 0.0632 AC XY: 4696 AN XY: 74276

African (AFR) AF: 0.0110 AC: 457 AN: 41482

American (AMR) AF: 0.0393 AC: 600 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3470

East Asian (EAS) AF: 0.0368 AC: 191 AN: 5184

South Asian (SAS) AF: 0.187 AC: 895 AN: 4786

European-Finnish (FIN) AF: 0.139 AC: 1461 AN: 10532

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0692 AC: 4706 AN: 67982

Other (OTH) AF: 0.0541 AC: 114 AN: 2108

Alfa AF: 0.0601 Hom.: 433

Bravo AF: 0.0455

Asia WGS AF: 0.0930 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.28
DANN	Benign	0.61
PhyloP100		-0.65
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: rs13073976; hg19: chr3-46286663;