Variant 3-46265274-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_178329.3(CCR3):c.116C>T(p.Pro39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,614,032 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0058 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 26 hom. )

Consequence

CCR3
NM_178329.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0310

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012571186).

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00326 (4760/1461762) while in subpopulation MID AF= 0.018 (104/5768). AF 95% confidence interval is 0.0152. There are 26 homozygotes in gnomad4_exome. There are 2411 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR3	NM_178329.3 linkuse as main transcript	c.116C>T	p.Pro39Leu	missense_variant	2/2	ENST00000395940.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR3	ENST00000395940.3 linkuse as main transcript	c.116C>T	p.Pro39Leu	missense_variant	2/2	1	NM_178329.3	P1	P51677-1

Frequencies

GnomAD3 genomes

AF:

0.00578

AC:

879

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00273

Gnomad OTH

AF:

0.00959

GnomAD3 exomes

AF:

0.00383

AC:

962

AN:

250988

Hom.:

AF XY:

0.00372

AC XY:

505

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.00892

Gnomad AMR exome

AF:

0.00663

Gnomad ASJ exome

AF:

0.0159

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00320

Gnomad OTH exome

AF:

0.00785

GnomAD4 exome

AF:

0.00326

AC:

4760

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

2411

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0124

Gnomad4 AMR exome

AF:

0.00725

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.00272

Gnomad4 OTH exome

AF:

0.00679

GnomAD4 genome

AF:

0.00577

AC:

878

AN:

152270

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

409

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0104

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00273

Gnomad4 OTH

AF:

0.00949

Alfa

AF:

0.00421

Hom.:

Bravo

AF:

0.00729

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00931

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00366

AC:

444

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00458

EpiControl

AF:

0.00504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;.;T;.;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.81

.;T;.;T;T

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

L;.;L;.;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-7.7

D;D;D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.013

D;D;D;D;D

Sift4G

Benign

0.36

T;T;T;T;T

Polyphen

0.87

P;.;P;P;P

Vest4

0.048

MVP

0.60

MPC

0.088

ClinPred

0.058

GERP RS

5.2

Varity_R

0.18

gMVP

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over