Genetic Variant NM_002089.4:c.*424G>A (chr4-74097332-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002089.4(CXCL2):c.*424G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 152,314 control chromosomes in the GnomAD database, including 20,489 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 0.49 ( 20468 hom., cov: 33)

Exomes 𝑓: 0.39 ( 21 hom. )

Consequence

CXCL2
NM_002089.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.273

Publications

26 publications found

Variant links:

Genes affected

CXCL2 (HGNC:4603): (C-X-C motif chemokine ligand 2) This antimicrobial gene is part of a chemokine superfamily that encodes secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CXC subfamily, is expressed at sites of inflammation and may suppress hematopoietic progenitor cell proliferation. [provided by RefSeq, Sep 2014]

CXCL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL2	NM_002089.4 link	c.*424G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000508487.3	NP_002080.1	P19875A0A024RDD9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL2	ENST00000508487.3 link	c.*424G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_002089.4	ENSP00000427279.1		P19875

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

74302

AN:

151870

Hom.:

20469

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.636

Gnomad AMR

AF:

0.621

Gnomad ASJ

AF:

0.582

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.520

Gnomad FIN

AF:

0.659

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.599

Gnomad OTH

AF:

0.513

GnomAD4 exome

AF:

0.390

AC:

127

AN:

326

Hom.:

Cov.:

AF XY:

0.409

AC XY:

AN XY:

176

show subpopulations

African (AFR)

AF:

0.0625

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.273

AC:

AN:

South Asian (SAS)

AF:

0.333

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.400

AC:

AN:

240

Other (OTH)

AF:

0.550

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.489

AC:

74309

AN:

151988

Hom.:

20468

Cov.:

AF XY:

0.494

AC XY:

36674

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.220

AC:

9118

AN:

41428

American (AMR)

AF:

0.621

AC:

9485

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.582

AC:

2018

AN:

3468

East Asian (EAS)

AF:

0.338

AC:

1746

AN:

5168

South Asian (SAS)

AF:

0.520

AC:

2508

AN:

4824

European-Finnish (FIN)

AF:

0.659

AC:

6950

AN:

10548

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.599

AC:

40676

AN:

67956

Other (OTH)

AF:

0.510

AC:

1074

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1730

3459

5189

6918

8648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

660

1320

1980

2640

3300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.563

Hom.:

95074

Bravo

AF:

0.476

Asia WGS

AF:

0.391

AC:

1363

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

2.1

(source)

DANN

Benign

0.68

PhyloP100

-0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over