Variant chr17-34256250-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_002982.4(CCL2):c.105T>C(p.Cys35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,609,614 control chromosomes in the GnomAD database, including 133,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.47 ( 18471 hom., cov: 32)

Exomes 𝑓: 0.39 ( 114846 hom. )

Consequence

CCL2
NM_002982.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.394

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]

CCL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-34256250-T-C is Benign according to our data. Variant chr17-34256250-T-C is described in ClinVar as [Benign]. Clinvar id is 3059105.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.394 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL2	NM_002982.4 linkuse as main transcript	c.105T>C	p.Cys35=	synonymous_variant	2/3	ENST00000225831.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CCL2	ENST00000225831.4 linkuse as main transcript	c.105T>C	p.Cys35=	synonymous_variant	2/3	1	NM_002982.4	P1
CCL2	ENST00000580907.6 linkuse as main transcript	c.105T>C	p.Cys35=	synonymous_variant	2/2	2
CCL2	ENST00000624362.2 linkuse as main transcript	n.966T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.474

AC:

72025

AN:

151884

Hom.:

18430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.665

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.539

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.557

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.409

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.359

Gnomad OTH

AF:

0.458

GnomAD3 exomes

AF:

0.444

AC:

111431

AN:

250930

Hom.:

26499

AF XY:

0.431

AC XY:

58446

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.676

Gnomad AMR exome

AF:

0.604

Gnomad ASJ exome

AF:

0.353

Gnomad EAS exome

AF:

0.554

Gnomad SAS exome

AF:

0.454

Gnomad FIN exome

AF:

0.414

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.403

GnomAD4 exome

AF:

0.388

AC:

565637

AN:

1457608

Hom.:

114846

Cov.:

AF XY:

0.388

AC XY:

281380

AN XY:

725212

show subpopulations

Gnomad4 AFR exome

AF:

0.676

Gnomad4 AMR exome

AF:

0.597

Gnomad4 ASJ exome

AF:

0.354

Gnomad4 EAS exome

AF:

0.611

Gnomad4 SAS exome

AF:

0.453

Gnomad4 FIN exome

AF:

0.408

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.403

GnomAD4 genome

AF:

0.474

AC:

72121

AN:

152006

Hom.:

18471

Cov.:

AF XY:

0.478

AC XY:

35499

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.665

Gnomad4 AMR

AF:

0.540

Gnomad4 ASJ

AF:

0.355

Gnomad4 EAS

AF:

0.557

Gnomad4 SAS

AF:

0.454

Gnomad4 FIN

AF:

0.409

Gnomad4 NFE

AF:

0.359

Gnomad4 OTH

AF:

0.455

Alfa

AF:

0.386

Hom.:

15264

Bravo

AF:

0.493

Asia WGS

AF:

0.508

AC:

1769

AN:

3478

EpiCase

AF:

0.357

EpiControl

AF:

0.359

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CCL2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.6

DANN

Benign

0.41

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over