3-46240900-T-C

Variant names:

• chr3-46240900-T-C
• rs12636651
• ENST00000357422.2:c.-67-1502T>C

Variant summary

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

The ENST00000357422.2(CCR3):​c.-67-1502T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,098 control chromosomes in the GnomAD database, including 8,314 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 0.32 (8314 hom., cov: 32)
• Consequence: CCR3 ENST00000357422.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 23 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR3	XM_006712960.4	c.-67-1502T>C		intron_variant	Intron 1 of 2		XP_006713023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR3	ENST00000357422.2	c.-67-1502T>C		intron_variant	Intron 2 of 3	2		ENSP00000350003.2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48592 AN: 151980 Hom.: 8292 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.320 AC: 48647 AN: 152098 Hom.: 8314 Cov.: 32 AF XY: 0.323 AC XY: 24040 AN XY: 74364

African (AFR) AF: 0.397 AC: 16494 AN: 41496

American (AMR) AF: 0.329 AC: 5037 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1115 AN: 3468

East Asian (EAS) AF: 0.605 AC: 3127 AN: 5166

South Asian (SAS) AF: 0.406 AC: 1952 AN: 4810

European-Finnish (FIN) AF: 0.263 AC: 2777 AN: 10572

Middle Eastern (MID) AF: 0.352 AC: 102 AN: 290

European-Non Finnish (NFE) AF: 0.252 AC: 17101 AN: 67988

Other (OTH) AF: 0.328 AC: 690 AN: 2106

Alfa AF: 0.285 Hom.: 13402

Bravo AF: 0.331

Asia WGS AF: 0.485 AC: 1685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.23
PhyloP100		0.16
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: rs12636651; hg19: chr3-46282391;