Variant 3-46358571-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001123396.4(CCR2):c.1044G>A(p.Thr348=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,601,034 control chromosomes in the GnomAD database, including 14,739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.096 ( 948 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13791 hom. )

Consequence

CCR2
NM_001123396.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.30

Variant links:

Genes affected

CCR2 (HGNC:1603): (C-C motif chemokine receptor 2) The protein encoded by this gene is a receptor for monocyte chemoattractant protein-1, a chemokine which specifically mediates monocyte chemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis as well as in the inflammatory response against tumors. The encoded protein mediates agonist-dependent calcium mobilization and inhibition of adenylyl cyclase. This protein can also be a coreceptor with CD4 for HIV-1 infection. This gene is located in the chemokine receptor gene cluster region of chromosome 3. [provided by RefSeq, Aug 2017]

CCR2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-46358571-G-A is Benign according to our data. Variant chr3-46358571-G-A is described in ClinVar as [Benign]. Clinvar id is 3060753.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR2	NM_001123396.4 linkuse as main transcript	c.1044G>A	p.Thr348=	synonymous_variant	2/2	ENST00000445132.3
CCR2	NM_001123041.3 linkuse as main transcript	c.941+103G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR2	ENST00000445132.3 linkuse as main transcript	c.1044G>A	p.Thr348=	synonymous_variant	2/2	1	NM_001123396.4	P2	P41597-2
CCR2	ENST00000400888.2 linkuse as main transcript	c.941+103G>A		intron_variant		1		A2	P41597-1
CCR2	ENST00000465202.1 linkuse as main transcript	n.769G>A		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.0956

AC:

14533

AN:

152070

Hom.:

948

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0276

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.0780

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0187

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.0727

GnomAD3 exomes

AF:

0.103

AC:

23117

AN:

224314

Hom.:

1531

AF XY:

0.102

AC XY:

12306

AN XY:

121228

show subpopulations

Gnomad AFR exome

AF:

0.0252

Gnomad AMR exome

AF:

0.0923

Gnomad ASJ exome

AF:

0.156

Gnomad EAS exome

AF:

0.000299

Gnomad SAS exome

AF:

0.0223

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.0964

GnomAD4 exome

AF:

0.131

AC:

189180

AN:

1448846

Hom.:

13791

Cov.:

AF XY:

0.127

AC XY:

91704

AN XY:

719326

show subpopulations

Gnomad4 AFR exome

AF:

0.0201

Gnomad4 AMR exome

AF:

0.0901

Gnomad4 ASJ exome

AF:

0.160

Gnomad4 EAS exome

AF:

0.000329

Gnomad4 SAS exome

AF:

0.0235

Gnomad4 FIN exome

AF:

0.149

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.0955

AC:

14539

AN:

152188

Hom.:

948

Cov.:

AF XY:

0.0930

AC XY:

6919

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0275

Gnomad4 AMR

AF:

0.0781

Gnomad4 ASJ

AF:

0.160

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0193

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.141

Gnomad4 OTH

AF:

0.0720

Alfa

AF:

0.124

Hom.:

672

Bravo

AF:

0.0881

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CCR2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

Cadd

Benign

0.62

Dann

Benign

0.52

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over