3-46357717-G-T

Variant names:

• chr3-46357717-G-T
• NM_001123396.4:c.190G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001123396.4(CCR2):​c.190G>T​(p.Val64Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCR2 NM_001123396.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR2	NM_001123396.4	c.190G>T	p.Val64Phe	missense_variant	Exon 2 of 2	ENST00000445132.3	NP_001116868.1
CCR2	NM_001123041.3	c.190G>T	p.Val64Phe	missense_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.190G>T	p.Val64Phe	missense_variant	Exon 2 of 2	1	NM_001123396.4	ENSP00000399285.2
CCR2	ENST00000400888.2	c.190G>T	p.Val64Phe	missense_variant	Exon 1 of 2	1		ENSP00000383681.2
CCR2	ENST00000421659.1	c.190G>T	p.Val64Phe	missense_variant	Exon 3 of 3	4		ENSP00000396736.1
CCR2	ENST00000465202.1	n.315-400G>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	.;T;.;T
Eigen	Benign	-0.097
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.85	D;T;T;.
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.3	M;M;.;M
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Uncertain	0.43
Sift	Benign	0.050	D;D;T;D
Sift4G	Uncertain	0.022	D;D;D;D
Polyphen		0.020	.;B;.;B
Vest4		0.41
MutPred		0.53		Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);
MVP		0.84
MPC		0.37
ClinPred		0.61	D
GERP RS		1.6
Varity_R		0.32
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-46399208;