4-73870427-A-G

Variant names:

• chr4-73870427-A-G
• rs4074
• NM_001511.4:c.309-94A>G

Variant summary

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

The NM_001511.4(CXCL1):​c.309-94A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,529,930 control chromosomes in the GnomAD database, including 281,115 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 0.47 (20505 hom., cov: 31)
  • Exomes 𝑓: 0.61 (260610 hom.)
• Consequence: CXCL1 NM_001511.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

Genes affected

CXCL1 (HGNC:4602): (C-X-C motif chemokine ligand 1) This antimicrobial gene encodes a member of the CXC subfamily of chemokines. The encoded protein is a secreted growth factor that signals through the G-protein coupled receptor, CXC receptor 2. This protein plays a role in inflammation and as a chemoattractant for neutrophils. Aberrant expression of this protein is associated with the growth and progression of certain tumors. A naturally occurring processed form of this protein has increased chemotactic activity. Alternate splicing results in coding and non-coding variants of this gene. A pseudogene of this gene is found on chromosome 4. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL1	NM_001511.4	c.309-94A>G		intron_variant	Intron 3 of 3	ENST00000395761.4	NP_001502.1
CXCL1	NR_046035.2	n.410-94A>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL1	ENST00000395761.4	c.309-94A>G		intron_variant	Intron 3 of 3	1	NM_001511.4	ENSP00000379110.3
CXCL1	ENST00000509101.1	n.*250A>G		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70828 AN: 151942 Hom.: 20511 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.606 AC: 835656 AN: 1377870 Hom.: 260610 AF XY: 0.605 AC XY: 415710 AN XY: 687054

Gnomad4 AFR exome AF: 0.0945

Gnomad4 AMR exome AF: 0.447

Gnomad4 ASJ exome AF: 0.501

Gnomad4 EAS exome AF: 0.523

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.631

Gnomad4 NFE exome AF: 0.644

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.466 AC: 70814 AN: 152060 Hom.: 20505 Cov.: 31 AF XY: 0.465 AC XY: 34577 AN XY: 74330

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.461

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.475

Alfa AF: 0.604 Hom.: 26391

Bravo AF: 0.437

Asia WGS AF: 0.482 AC: 1675 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	3.0
DANN	Benign	0.71

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: rs4074; hg19: chr4-74736144; COSMIC: COSV67611568; COSMIC: COSV67611568;