17-34256892-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002982.4(CCL2):​c.*65C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 923,064 control chromosomes in the GnomAD database, including 45,576 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 0.29 ( 6917 hom., cov: 32)
Exomes 𝑓: 0.30 ( 38659 hom. )

Consequence

CCL2
NM_002982.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.224
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
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
CCL2NM_002982.4 linkuse as main transcriptc.*65C>T 3_prime_UTR_variant 3/3 ENST00000225831.4 NP_002973.1 P13500

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCL2ENST00000225831.4 linkuse as main transcriptc.*65C>T 3_prime_UTR_variant 3/31 NM_002982.4 ENSP00000225831.4 P13500
CCL2ENST00000580907.6 linkuse as main transcriptc.*549C>T 3_prime_UTR_variant 2/22 ENSP00000462156.1 J3KRT7
CCL2ENST00000624362.2 linkuse as main transcriptn.1608C>T non_coding_transcript_exon_variant 1/16

Frequencies

GnomAD3 genomes
AF:
0.287
AC:
43568
AN:
151918
Hom.:
6905
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.202
Gnomad AMI
AF:
0.140
Gnomad AMR
AF:
0.430
Gnomad ASJ
AF:
0.282
Gnomad EAS
AF:
0.555
Gnomad SAS
AF:
0.342
Gnomad FIN
AF:
0.344
Gnomad MID
AF:
0.326
Gnomad NFE
AF:
0.275
Gnomad OTH
AF:
0.285
GnomAD4 exome
AF:
0.298
AC:
229448
AN:
771026
Hom.:
38659
Cov.:
10
AF XY:
0.298
AC XY:
119827
AN XY:
402548
show subpopulations
Gnomad4 AFR exome
AF:
0.191
Gnomad4 AMR exome
AF:
0.512
Gnomad4 ASJ exome
AF:
0.281
Gnomad4 EAS exome
AF:
0.619
Gnomad4 SAS exome
AF:
0.334
Gnomad4 FIN exome
AF:
0.343
Gnomad4 NFE exome
AF:
0.258
Gnomad4 OTH exome
AF:
0.290
GnomAD4 genome
AF:
0.287
AC:
43608
AN:
152038
Hom.:
6917
Cov.:
32
AF XY:
0.296
AC XY:
21971
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.202
Gnomad4 AMR
AF:
0.431
Gnomad4 ASJ
AF:
0.282
Gnomad4 EAS
AF:
0.555
Gnomad4 SAS
AF:
0.343
Gnomad4 FIN
AF:
0.344
Gnomad4 NFE
AF:
0.275
Gnomad4 OTH
AF:
0.284
Alfa
AF:
0.271
Hom.:
5428
Bravo
AF:
0.290
Asia WGS
AF:
0.440
AC:
1529
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
6.8
DANN
Benign
0.63

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs13900; hg19: chr17-32583911; COSMIC: COSV56773543; COSMIC: COSV56773543; API