rs28730833

Variant names:

• chr17-34255475-T-A
• rs28730833
• NM_002982.4:c.76+50T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

CCL2 Gene-Disease associations (from GenCC):

• neural tube defects, susceptibility to

  Inheritance: AD Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1448 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL2	NM_002982.4	c.76+50T>A		intron_variant	Intron 1 of 2	ENST00000225831.4	NP_002973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL2	ENST00000225831.4	c.76+50T>A		intron_variant	Intron 1 of 2	1	NM_002982.4	ENSP00000225831.4
CCL2	ENST00000624362.2	n.191T>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
CCL2	ENST00000580907.6	c.76+50T>A		intron_variant	Intron 1 of 1	2		ENSP00000462156.1

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

GnomAD2 exomes AF: 0.0149 AC: 3669 AN: 246384 AF XY: 0.0164

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 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

African (AFR) AF: 0.00256 AC: 78 AN: 30450

American (AMR) AF: 0.00813 AC: 355 AN: 43648

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 719 AN: 24984

East Asian (EAS) AF: 0.0107 AC: 418 AN: 38936

South Asian (SAS) AF: 0.0395 AC: 3270 AN: 82804

European-Finnish (FIN) AF: 0.00122 AC: 64 AN: 52666

Middle Eastern (MID) AF: 0.0172 AC: 94 AN: 5472

European-Non Finnish (NFE) AF: 0.0128 AC: 12544 AN: 980806

Other (OTH) AF: 0.0145 AC: 804 AN: 55598

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

African (AFR) AF: 0.00226 AC: 94 AN: 41550

American (AMR) AF: 0.00608 AC: 93 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3472

East Asian (EAS) AF: 0.0165 AC: 85 AN: 5160

South Asian (SAS) AF: 0.0394 AC: 190 AN: 4818

European-Finnish (FIN) AF: 0.000660 AC: 7 AN: 10610

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0125 AC: 853 AN: 68024

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

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
PhyloP100		-0.68
PromoterAI		-0.0076	Neutral
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: rs28730833; hg19: chr17-32582494;