Genetic Variant CCR3:c.-11-1198C>A (chr3-46263950-C-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.-11-1198C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 155,710 control chromosomes in the GnomAD database, including 468 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 0.068 ( 456 hom., cov: 32)

Exomes 𝑓: 0.074 ( 12 hom. )

Consequence

CCR3
NM_178329.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0790

Publications

7 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:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR3	NM_178329.3 link	c.-11-1198C>A		intron_variant	Intron 1 of 1	ENST00000395940.3	NP_847899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR3	ENST00000395940.3 link	c.-11-1198C>A		intron_variant	Intron 1 of 1	1	NM_178329.3	ENSP00000379271.2

Frequencies

GnomAD3 genomes

AF:

0.0685

AC:

10424

AN:

152158

Hom.:

458

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0473

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0446

Gnomad ASJ

AF:

0.0634

Gnomad EAS

AF:

0.0362

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0690

Gnomad OTH

AF:

0.0664

GnomAD4 exome

AF:

0.0740

AC:

254

AN:

3434

Hom.:

Cov.:

AF XY:

0.0815

AC XY:

142

AN XY:

1742

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0492

AC:

AN:

244

Ashkenazi Jewish (ASJ)

AF:

0.0952

AC:

AN:

East Asian (EAS)

AF:

0.0208

AC:

AN:

South Asian (SAS)

AF:

0.165

AC:

AN:

322

European-Finnish (FIN)

AF:

0.129

AC:

AN:

140

Middle Eastern (MID)

AF:

0.0833

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0648

AC:

156

AN:

2406

Other (OTH)

AF:

0.0450

AC:

AN:

200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0685

AC:

10425

AN:

152276

Hom.:

456

Cov.:

AF XY:

0.0736

AC XY:

5481

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0474

AC:

1970

AN:

41576

American (AMR)

AF:

0.0445

AC:

680

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0634

AC:

220

AN:

3472

East Asian (EAS)

AF:

0.0363

AC:

188

AN:

5182

South Asian (SAS)

AF:

0.190

AC:

915

AN:

4820

European-Finnish (FIN)

AF:

0.139

AC:

1475

AN:

10598

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0690

AC:

4694

AN:

68014

Other (OTH)

AF:

0.0653

AC:

138

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

483

966

1448

1931

2414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0680

Hom.:

108

Bravo

AF:

0.0577

Asia WGS

AF:

0.0920

AC:

318

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.4

(source)

DANN

Benign

0.42

PhyloP100

-0.079

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