chr3-46355125-G-A

Variant names:

• chr3-46355125-G-A
• rs3762823
• NM_001123396.4:c.-52+948G>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.-52+948G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,190 control chromosomes in the GnomAD database, including 3,427 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 (3427 hom., cov: 32)
• Consequence: CCR2 NM_001123396.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCR2	NM_001123396.4	c.-52+948G>A		intron_variant	Intron 1 of 1	ENST00000445132.3	NP_001116868.1
CCR2	NM_001123041.3	c.-52+948G>A		intron_variant	Intron 1 of 2		NP_001116513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCR2	ENST00000445132.3	c.-52+948G>A		intron_variant	Intron 1 of 1	1	NM_001123396.4	ENSP00000399285.2
CCR2	ENST00000421659.1	c.-52+169G>A		intron_variant	Intron 2 of 2	4		ENSP00000396736.1
CCR2	ENST00000465202.1	n.314+948G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30440 AN: 152072 Hom.: 3423 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.235

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.200 AC: 30442 AN: 152190 Hom.: 3427 Cov.: 32 AF XY: 0.199 AC XY: 14788 AN XY: 74414

African (AFR) AF: 0.104 AC: 4313 AN: 41522

American (AMR) AF: 0.292 AC: 4462 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3468

East Asian (EAS) AF: 0.278 AC: 1438 AN: 5180

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

European-Finnish (FIN) AF: 0.152 AC: 1614 AN: 10590

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16394 AN: 67992

Other (OTH) AF: 0.234 AC: 493 AN: 2108

Alfa AF: 0.197 Hom.: 373

Bravo AF: 0.206

Asia WGS AF: 0.200 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.46
PhyloP100		0.24
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: rs3762823; hg19: chr3-46396616;