3-46253466-C-T

Variant names:

• chr3-46253466-C-T
• rs9854964
• NM_178329.3:c.-12+10928C>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.-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 NM_178329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178329.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR3	NM_178329.3	MANE Select	c.-12+10928C>T		intron	N/A	NP_847899.1
	CCR3	NM_178328.1		c.-17-10921C>T		intron	N/A	NP_847898.1
	CCR3	NM_001164680.2		c.-17-10921C>T		intron	N/A	NP_001158152.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR3	ENST00000395940.3	TSL:1 MANE Select	c.-12+10928C>T		intron	N/A	ENSP00000379271.2
	CCR3	ENST00000545097.1	TSL:1	c.-17-10921C>T		intron	N/A	ENSP00000441600.1
	CCR3	ENST00000452454.1	TSL:1	c.-80-10921C>T		intron	N/A	ENSP00000389336.1

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

African (AFR) AF: 0.574 AC: 23784 AN: 41418

American (AMR) AF: 0.403 AC: 6160 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1436 AN: 3468

East Asian (EAS) AF: 0.641 AC: 3306 AN: 5160

South Asian (SAS) AF: 0.615 AC: 2961 AN: 4818

European-Finnish (FIN) AF: 0.402 AC: 4229 AN: 10532

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22045 AN: 67936

Other (OTH) AF: 0.441 AC: 931 AN: 2110

Alfa AF: 0.398 Hom.: 3761

Bravo AF: 0.437

Asia WGS AF: 0.602 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.59
PhyloP100		-2.6
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: rs9854964; hg19: chr3-46294957;