rs3749461

Variant names:

• chr3-46353822-A-G
• rs3749461
• ENST00000465202.1:n.-42A>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	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;