3-46357683-G-C

Variant names:

• chr3-46357683-G-C
• rs3918367
• NM_001123396.4:c.156G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001123396.4(CCR2):​c.156G>C​(p.Val52Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V52V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCR2 NM_001123396.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.132 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR2	NM_001123396.4	c.156G>C	p.Val52Val	synonymous_variant	Exon 2 of 2	ENST00000445132.3	NP_001116868.1
CCR2	NM_001123041.3	c.156G>C	p.Val52Val	synonymous_variant	Exon 2 of 3		NP_001116513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR2	ENST00000445132.3	c.156G>C	p.Val52Val	synonymous_variant	Exon 2 of 2	1	NM_001123396.4	ENSP00000399285.2
CCR2	ENST00000400888.2	c.156G>C	p.Val52Val	synonymous_variant	Exon 1 of 2	1		ENSP00000383681.2
CCR2	ENST00000421659.1	c.156G>C	p.Val52Val	synonymous_variant	Exon 3 of 3	4		ENSP00000396736.1
CCR2	ENST00000465202.1	n.315-434G>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.7
DANN	Benign	0.62
PhyloP100		0.13
PromoterAI		0.0023	Neutral

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: rs3918367; hg19: chr3-46399174;