chr3-46357717-G-T

Variant names:

• chr3-46357717-G-T
• rs1799864
• NM_001123396.4:c.190G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001123041.3(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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V64I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCR2 NM_001123041.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123041.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR2	NM_001123396.4	MANE Select	c.190G>T	p.Val64Phe	missense	Exon 2 of 2	NP_001116868.1
	CCR2	NM_001123041.3		c.190G>T	p.Val64Phe	missense	Exon 2 of 3	NP_001116513.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCR2	ENST00000445132.3	TSL:1 MANE Select	c.190G>T	p.Val64Phe	missense	Exon 2 of 2	ENSP00000399285.2
	CCR2	ENST00000400888.2	TSL:1	c.190G>T	p.Val64Phe	missense	Exon 1 of 2	ENSP00000383681.2
	CCR2	ENST00000908302.1		c.190G>T	p.Val64Phe	missense	Exon 2 of 2	ENSP00000578361.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.097
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.1
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.43
Sift	Benign	0.050	D
Sift4G	Uncertain	0.022	D
Polyphen		0.020	B
Vest4		0.41
MutPred		0.53		Loss of sheet (P = 0.1501)
MVP		0.84
MPC		0.37
ClinPred		0.61	D
GERP RS		1.6
PromoterAI		-0.0036	Neutral
Varity_R		0.32
gMVP		0.74
Mutation Taster		=72/28	polymorphism

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: rs1799864; hg19: chr3-46399208;