3-46358571-G-A

Variant names:

• chr3-46358571-G-A
• rs3092960
• NM_001123396.4:c.1044G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001123396.4(CCR2):​c.1044G>A​(p.Thr348Thr) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.096 (948 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13791 hom.)
• Consequence: CCR2 NM_001123396.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.30
• Publications: 16 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 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 no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
CCR2	NM_001123396.4	c.1044G>A	p.Thr348Thr	synonymous_variant	Exon 2 of 2	ENST00000445132.3	NP_001116868.1
CCR2	NM_001123041.3	c.941+103G>A		intron_variant	Intron 2 of 2		NP_001116513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR2	ENST00000445132.3	c.1044G>A	p.Thr348Thr	synonymous_variant	Exon 2 of 2	1	NM_001123396.4	ENSP00000399285.2
CCR2	ENST00000400888.2	c.941+103G>A		intron_variant	Intron 1 of 1	1		ENSP00000383681.2
CCR2	ENST00000465202.1	n.769G>A		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14533 AN: 152070 Hom.: 948 Cov.: 32

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

GnomAD2 exomes AF: 0.103 AC: 23117 AN: 224314 AF XY: 0.102

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 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.: 35 AF XY: 0.127 AC XY: 91704 AN XY: 719326

African (AFR) AF: 0.0201 AC: 670 AN: 33320

American (AMR) AF: 0.0901 AC: 3805 AN: 42242

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 4118 AN: 25674

East Asian (EAS) AF: 0.000329 AC: 13 AN: 39466

South Asian (SAS) AF: 0.0235 AC: 1994 AN: 84758

European-Finnish (FIN) AF: 0.149 AC: 7813 AN: 52534

Middle Eastern (MID) AF: 0.0224 AC: 129 AN: 5762

European-Non Finnish (NFE) AF: 0.148 AC: 163865 AN: 1105116

Other (OTH) AF: 0.113 AC: 6773 AN: 59974

GnomAD4 genome AF: 0.0955 AC: 14539 AN: 152188 Hom.: 948 Cov.: 32 AF XY: 0.0930 AC XY: 6919 AN XY: 74390

African (AFR) AF: 0.0275 AC: 1144 AN: 41554

American (AMR) AF: 0.0781 AC: 1193 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3468

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4816

European-Finnish (FIN) AF: 0.151 AC: 1600 AN: 10576

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9609 AN: 67988

Other (OTH) AF: 0.0720 AC: 152 AN: 2112

Alfa AF: 0.123 Hom.: 673

Bravo AF: 0.0881

Asia WGS AF: 0.0200 AC: 72 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CCR2-related disorder Benign:1

Oct 31, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
PhyloP100		-1.3
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs3092960; hg19: chr3-46400062;