rs743660

Variant names:

• chr3-46360527-G-A
• rs743660
• NM_001123396.4:c.*1917G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001123396.4(CCR2):​c.*1917G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,258 control chromosomes in the GnomAD database, including 3,423 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 0.20 (3423 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCR2 NM_001123396.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 17 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR2	NM_001123396.4	c.*1917G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000445132.3	NP_001116868.1
CCR2	NM_001123041.3	c.*667G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001116513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR2	ENST00000445132.3	c.*1917G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_001123396.4	ENSP00000399285.2
CCR2	ENST00000400888.2	c.*667G>A		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000383681.2

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30427 AN: 152140 Hom.: 3419 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.235

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.200 AC: 30429 AN: 152258 Hom.: 3423 Cov.: 33 AF XY: 0.199 AC XY: 14779 AN XY: 74452

African (AFR) AF: 0.104 AC: 4312 AN: 41548

American (AMR) AF: 0.292 AC: 4459 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 731 AN: 3468

East Asian (EAS) AF: 0.278 AC: 1443 AN: 5190

South Asian (SAS) AF: 0.157 AC: 757 AN: 4828

European-Finnish (FIN) AF: 0.153 AC: 1618 AN: 10600

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16379 AN: 68010

Other (OTH) AF: 0.233 AC: 493 AN: 2114

Alfa AF: 0.224 Hom.: 6209

Bravo AF: 0.206

Asia WGS AF: 0.200 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.71
PhyloP100		-0.027
Mutation Taster		=100/0	polymorphism (auto)

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: rs743660; hg19: chr3-46402018;