3-46259057-G-T

Variant names:

• chr3-46259057-G-T
• rs9811301
• NM_178329.3:c.-11-6091G>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.-11-6091G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,676 control chromosomes in the GnomAD database, including 10,740 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 0.37 (10740 hom., cov: 32)
• Consequence: CCR3 NM_178329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• Publications: 0 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 = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR3	NM_178329.3	c.-11-6091G>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.-11-6091G>T		intron_variant	Intron 1 of 1	1	NM_178329.3	ENSP00000379271.2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56190 AN: 151558 Hom.: 10710 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.371 AC: 56259 AN: 151676 Hom.: 10740 Cov.: 32 AF XY: 0.380 AC XY: 28168 AN XY: 74082

African (AFR) AF: 0.370 AC: 15283 AN: 41358

American (AMR) AF: 0.385 AC: 5874 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1430 AN: 3462

East Asian (EAS) AF: 0.634 AC: 3257 AN: 5140

South Asian (SAS) AF: 0.614 AC: 2955 AN: 4816

European-Finnish (FIN) AF: 0.398 AC: 4169 AN: 10484

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.323 AC: 21936 AN: 67874

Other (OTH) AF: 0.401 AC: 843 AN: 2104

Alfa AF: 0.351 Hom.: 1228

Bravo AF: 0.372

Asia WGS AF: 0.590 AC: 2048 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.27
PhyloP100		-0.54
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: rs9811301; hg19: chr3-46300548;