rs2857657

Positions:

• chr17-34256113-G-C
• chr17-34256113-G-T

Variant summary

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

The NM_002982.4(CCL2):​c.77-109G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 715,820 control chromosomes in the GnomAD database, including 252,363 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 0.86 (56729 hom., cov: 33)
  • Exomes 𝑓: 0.83 (195634 hom.)
• Consequence: CCL2 NM_002982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

Genes affected

CCL2 (HGNC:10618): (C-C motif chemokine ligand 2) This gene is one of several cytokine genes clustered on the q-arm of chromosome 17. Chemokines are a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide. This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes and basophils but not for neutrophils or eosinophils. It has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis and atherosclerosis. It binds to chemokine receptors CCR2 and CCR4. Elevated expression of the encoded protein is associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. [provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL2	NM_002982.4	c.77-109G>C		intron_variant		ENST00000225831.4	NP_002973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL2	ENST00000225831.4	c.77-109G>C		intron_variant		1	NM_002982.4	ENSP00000225831	P1
CCL2	ENST00000580907.6	c.77-109G>C		intron_variant		2		ENSP00000462156
CCL2	ENST00000624362.2	n.829G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130873 AN: 152130 Hom.: 56664 Cov.: 33

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.839

GnomAD4 exome AF: 0.831 AC: 468539 AN: 563572 Hom.: 195634 Cov.: 7 AF XY: 0.834 AC XY: 249084 AN XY: 298758

Gnomad4 AFR exome AF: 0.956

Gnomad4 AMR exome AF: 0.896

Gnomad4 ASJ exome AF: 0.834

Gnomad4 EAS exome AF: 0.930

Gnomad4 SAS exome AF: 0.912

Gnomad4 FIN exome AF: 0.834

Gnomad4 NFE exome AF: 0.797

Gnomad4 OTH exome AF: 0.828

GnomAD4 genome AF: 0.860 AC: 131000 AN: 152248 Hom.: 56729 Cov.: 33 AF XY: 0.865 AC XY: 64340 AN XY: 74422

Gnomad4 AFR AF: 0.956

Gnomad4 AMR AF: 0.869

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.919

Gnomad4 SAS AF: 0.916

Gnomad4 FIN AF: 0.836

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.839

Alfa AF: 0.842 Hom.: 6690

Bravo AF: 0.864

Asia WGS AF: 0.926 AC: 3220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.71

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: rs2857657; hg19: chr17-32583132;