rs3917887

Positions:

• chr17-34255978-ACAGCTCCTCCTTCT-A
• chr17-34255978-ACAGCTCCTCCTTCT-ACAGCTCCTCCTTCTCAGCTCCTCCTTCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002982.4(CCL2):​c.77-242_77-229del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 451,188 control chromosomes in the GnomAD database, including 26,054 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8997 hom., cov: 0)
  • Exomes 𝑓: 0.33 (17057 hom.)
• Consequence: CCL2 NM_002982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL2	NM_002982.4	c.77-242_77-229del		intron_variant		ENST00000225831.4	NP_002973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL2	ENST00000225831.4	c.77-242_77-229del		intron_variant		1	NM_002982.4	ENSP00000225831	P1
CCL2	ENST00000580907.6	c.77-242_77-229del		intron_variant		2		ENSP00000462156
CCL2	ENST00000624362.2	n.696_709del		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50725 AN: 151932 Hom.: 8976 Cov.: 0

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.326 AC: 97486 AN: 299136 Hom.: 17057 AF XY: 0.325 AC XY: 50575 AN XY: 155780

Gnomad4 AFR exome AF: 0.380

Gnomad4 AMR exome AF: 0.498

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.624

Gnomad4 SAS exome AF: 0.340

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.318

GnomAD4 genome AF: 0.334 AC: 50790 AN: 152052 Hom.: 8997 Cov.: 0 AF XY: 0.340 AC XY: 25300 AN XY: 74324

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.319

Alfa AF: 0.298 Hom.: 819

Bravo AF: 0.344

Asia WGS AF: 0.450 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3917887; hg19: chr17-32582997;