rs28730833

chr17-34255475-T-Achr17-34255475-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002982.4(CCL2):c.76+50T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,467,604 control chromosomes in the GnomAD database, including 238 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 0.0095 (13 hom., cov: 32)
  • Exomes 𝑓: 0.014 (225 hom.)
• Consequence: CCL2 NM_002982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682

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=-0.83).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00951 (1448/152240) while in subpopulation SAS AF= 0.0394 (190/4818). AF 95% confidence interval is 0.0349. There are 13 homozygotes in gnomad4. There are 710 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1447 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL2	NM_002982.4	c.76+50T>A		intron_variant		ENST00000225831.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL2	ENST00000225831.4	c.76+50T>A		intron_variant		1	NM_002982.4	P1
CCL2	ENST00000580907.6	c.76+50T>A		intron_variant		2
CCL2	ENST00000624362.2	n.191T>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00951 AC: 1447 AN: 152120 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.0149 AC: 3669 AN: 246384 Hom.: 64 AF XY: 0.0164 AC XY: 2185 AN XY: 133250

Gnomad AFR exome AF: 0.00192

Gnomad AMR exome AF: 0.00835

Gnomad ASJ exome AF: 0.0291

Gnomad EAS exome AF: 0.0154

Gnomad SAS exome AF: 0.0398

Gnomad FIN exome AF: 0.00114

Gnomad NFE exome AF: 0.0133

Gnomad OTH exome AF: 0.0153

GnomAD4 exome AF: 0.0139 AC: 18346 AN: 1315364 Hom.: 225 Cov.: 19 AF XY: 0.0147 AC XY: 9720 AN XY: 662194

Gnomad4 AFR exome AF: 0.00256

Gnomad4 AMR exome AF: 0.00813

Gnomad4 ASJ exome AF: 0.0288

Gnomad4 EAS exome AF: 0.0107

Gnomad4 SAS exome AF: 0.0395

Gnomad4 FIN exome AF: 0.00122

Gnomad4 NFE exome AF: 0.0128

Gnomad4 OTH exome AF: 0.0145

GnomAD4 genome AF: 0.00951 AC: 1448 AN: 152240 Hom.: 13 Cov.: 32 AF XY: 0.00954 AC XY: 710 AN XY: 74434

Gnomad4 AFR AF: 0.00226

Gnomad4 AMR AF: 0.00608

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.0165

Gnomad4 SAS AF: 0.0394

Gnomad4 FIN AF: 0.000660

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0127 Hom.: 2

Bravo AF: 0.00935

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.78
Dann	Benign	0.73

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: rs28730833; hg19: chr17-32582494;