4-74097332-C-T

Position:

• chr4-74097332-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000508487.3(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 ENST00000508487.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CXCL2	NM_002089.4	c.*424G>A		3_prime_UTR_variant	4/4	ENST00000508487.3	NP_002080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL2	ENST00000508487.3	c.*424G>A		3_prime_UTR_variant	4/4	1	NM_002089.4	ENSP00000427279	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74302 AN: 151870 Hom.: 20469 Cov.: 33

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.: 21 Cov.: 0 AF XY: 0.409 AC XY: 72 AN XY: 176

Gnomad4 AFR exome AF: 0.0625

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.550

GnomAD4 genome AF: 0.489 AC: 74309 AN: 151988 Hom.: 20468 Cov.: 33 AF XY: 0.494 AC XY: 36674 AN XY: 74262

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.510

Alfa AF: 0.580 Hom.: 42462

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
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9131; hg19: chr4-74963049;