rs3749461

Positions:

• chr3-46353822-A-G

Variant summary

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

The ENST00000465202.1(CCR2):​n.-42A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 152,190 control chromosomes in the GnomAD database, including 392 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 0.057 (392 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCR2 ENST00000465202.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

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 = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCR2	ENST00000465202.1	n.-42A>G		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0568 AC: 8634 AN: 152074 Hom.: 393 Cov.: 31

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0680

Gnomad OTH AF: 0.0542

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0567 AC: 8626 AN: 152190 Hom.: 392 Cov.: 31 AF XY: 0.0623 AC XY: 4634 AN XY: 74404

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.0341

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.0344

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.0680

Gnomad4 OTH AF: 0.0531

Alfa AF: 0.0592 Hom.: 51

Bravo AF: 0.0436

Asia WGS AF: 0.0910 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.4
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs3749461; hg19: chr3-46395313;