rs3138042

chr3-46359541-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001123396.4(CCR2):c.*931A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,043,916 control chromosomes in the GnomAD database, including 51,376 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (7817 hom., cov: 32)
  • Exomes 𝑓: 0.31 (43559 hom.)
• Consequence: CCR2 NM_001123396.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCR2	NM_001123396.4	c.*931A>G		3_prime_UTR_variant	2/2	ENST00000445132.3
CCR2	NM_001123041.3	c.942-136A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCR2	ENST00000445132.3	c.*931A>G		3_prime_UTR_variant	2/2	1	NM_001123396.4	P2
CCR2	ENST00000400888.2	c.942-136A>G		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48561 AN: 151798 Hom.: 7800 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.309 AC: 275829 AN: 892002 Hom.: 43559 Cov.: 12 AF XY: 0.311 AC XY: 138647 AN XY: 445868

Gnomad4 AFR exome AF: 0.332

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.270

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.307

Gnomad4 OTH exome AF: 0.319

GnomAD4 genome AF: 0.320 AC: 48596 AN: 151914 Hom.: 7817 Cov.: 32 AF XY: 0.322 AC XY: 23921 AN XY: 74248

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.355

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.334

Alfa AF: 0.301 Hom.: 1396

Bravo AF: 0.323

Asia WGS AF: 0.309 AC: 1073 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	6.4
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs3138042; hg19: chr3-46401032; COSMIC: COSV52748969; COSMIC: COSV52748969;