3-46253466-C-T

Position:

• chr3-46253466-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000395940.3(CCR3):​c.-12+10928C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,918 control chromosomes in the GnomAD database, including 15,104 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 0.43 (15104 hom., cov: 31)
• Consequence: CCR3 ENST00000395940.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCR3	NM_178329.3	c.-12+10928C>T		intron_variant		ENST00000395940.3	NP_847899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR3	ENST00000395940.3	c.-12+10928C>T		intron_variant		1	NM_178329.3	ENSP00000379271	P1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65298 AN: 151800 Hom.: 15069 Cov.: 31

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.430 AC: 65375 AN: 151918 Hom.: 15104 Cov.: 31 AF XY: 0.438 AC XY: 32495 AN XY: 74234

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.441

Alfa AF: 0.385 Hom.: 1498

Bravo AF: 0.437

Asia WGS AF: 0.602 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs9854964; hg19: chr3-46294957;