3-46264639-G-T

Variant names:

• chr3-46264639-G-T
• rs3091250
• NM_178329.3:c.-11-509G>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.-11-509G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 538,288 control chromosomes in the GnomAD database, including 24,675 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 0.27 (5969 hom., cov: 31)
  • Exomes 𝑓: 0.29 (18706 hom.)
• Consequence: CCR3 NM_178329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451
• Publications: 9 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 = 0.586 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR3	NM_178329.3	MANE Select	c.-11-509G>T		intron	N/A	NP_847899.1	P51677-1
	CCR3	NM_178328.1		c.52+184G>T		intron	N/A	NP_847898.1	P51677-2
	CCR3	NM_001164680.2		c.43+193G>T		intron	N/A	NP_001158152.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR3	ENST00000395940.3	TSL:1 MANE Select	c.-11-509G>T		intron	N/A	ENSP00000379271.2	P51677-1
	CCR3	ENST00000545097.1	TSL:1	c.52+184G>T		intron	N/A	ENSP00000441600.1	P51677-2
	CCR3	ENST00000452454.1	TSL:1	c.-12+184G>T		intron	N/A	ENSP00000389336.1	Q8TDP5

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40862 AN: 151582 Hom.: 5948 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.295 AC: 114020 AN: 386592 Hom.: 18706 Cov.: 0 AF XY: 0.301 AC XY: 61897 AN XY: 205716

African (AFR) AF: 0.222 AC: 1887 AN: 8512

American (AMR) AF: 0.344 AC: 3841 AN: 11174

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 3942 AN: 12120

East Asian (EAS) AF: 0.588 AC: 14083 AN: 23956

South Asian (SAS) AF: 0.405 AC: 14936 AN: 36854

European-Finnish (FIN) AF: 0.268 AC: 7317 AN: 27252

Middle Eastern (MID) AF: 0.388 AC: 730 AN: 1880

European-Non Finnish (NFE) AF: 0.251 AC: 60642 AN: 242064

Other (OTH) AF: 0.292 AC: 6642 AN: 22780

GnomAD4 genome AF: 0.270 AC: 40916 AN: 151696 Hom.: 5969 Cov.: 31 AF XY: 0.276 AC XY: 20417 AN XY: 74102

African (AFR) AF: 0.220 AC: 9098 AN: 41336

American (AMR) AF: 0.313 AC: 4777 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3470

East Asian (EAS) AF: 0.603 AC: 3116 AN: 5164

South Asian (SAS) AF: 0.423 AC: 2028 AN: 4794

European-Finnish (FIN) AF: 0.264 AC: 2764 AN: 10480

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17035 AN: 67896

Other (OTH) AF: 0.296 AC: 623 AN: 2106

Alfa AF: 0.251 Hom.: 1490

Bravo AF: 0.273

Asia WGS AF: 0.482 AC: 1668 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.21
PhyloP100		0.45
PromoterAI		0.0041	Neutral
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3091250;

hg19: chr3-46306130;