dbSNP rs9853223: CCR3:c.-12+64G>A (chr3-46242602-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178329.3(CCR3):c.-12+64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,774 control chromosomes in the GnomAD database, including 14,794 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 0.44 ( 14794 hom., cov: 29)

Exomes 𝑓: 0.083 ( 0 hom. )

Consequence

CCR3
NM_178329.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.213

Publications

10 publications found

Variant links:

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]

CCR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR3	NM_178329.3 link	c.-12+64G>A		intron_variant	Intron 1 of 1	ENST00000395940.3	NP_847899.1	P51677-1A1LPE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR3	ENST00000395940.3 link	c.-12+64G>A		intron_variant	Intron 1 of 1	1	NM_178329.3	ENSP00000379271.2		P51677-1

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

66655

AN:

151644

Hom.:

14770

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.439

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.436

Gnomad OTH

AF:

0.433

GnomAD4 exome

AF:

0.0833

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.100

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.440

AC:

66716

AN:

151762

Hom.:

14794

Cov.:

AF XY:

0.439

AC XY:

32556

AN XY:

74136

show subpopulations

African (AFR)

AF:

0.468

AC:

19334

AN:

41324

American (AMR)

AF:

0.446

AC:

6804

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

1525

AN:

3470

East Asian (EAS)

AF:

0.310

AC:

1595

AN:

5152

South Asian (SAS)

AF:

0.373

AC:

1796

AN:

4816

European-Finnish (FIN)

AF:

0.434

AC:

4560

AN:

10506

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.436

AC:

29612

AN:

67926

Other (OTH)

AF:

0.429

AC:

903

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1837

3673

5510

7346

9183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.432

Hom.:

8557

Bravo

AF:

0.441

Asia WGS

AF:

0.347

AC:

1206

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

0.28

(source)

DANN

Benign

0.27

PhyloP100

-0.21

PromoterAI

-0.026

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over