3-46263115-C-T

Variant names:

• chr3-46263115-C-T
• rs1491962
• NM_178329.3:c.-11-2033C>T

Variant summary

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

The NM_178329.3(CCR3):​c.-11-2033C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,092 control chromosomes in the GnomAD database, including 23,355 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 0.54 (23355 hom., cov: 33)
• Consequence: CCR3 NM_178329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631
• Publications: 14 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR3	NM_178329.3	c.-11-2033C>T		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.-11-2033C>T		intron_variant	Intron 1 of 1	1	NM_178329.3	ENSP00000379271.2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82559 AN: 151974 Hom.: 23325 Cov.: 33

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.543 AC: 82632 AN: 152092 Hom.: 23355 Cov.: 33 AF XY: 0.554 AC XY: 41199 AN XY: 74352

African (AFR) AF: 0.420 AC: 17422 AN: 41466

American (AMR) AF: 0.651 AC: 9947 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2080 AN: 3464

East Asian (EAS) AF: 0.904 AC: 4688 AN: 5186

South Asian (SAS) AF: 0.762 AC: 3677 AN: 4828

European-Finnish (FIN) AF: 0.548 AC: 5785 AN: 10550

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37024 AN: 67996

Other (OTH) AF: 0.597 AC: 1262 AN: 2114

Alfa AF: 0.553 Hom.: 35206

Bravo AF: 0.543

Asia WGS AF: 0.783 AC: 2721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.63
DANN	Benign	0.63
PhyloP100		-0.63
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: rs1491962; hg19: chr3-46304606;