4-73870427-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 38 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001511.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL1	NM_001511.4	MANE Select	c.309-94A>G		intron	N/A	NP_001502.1	P09341
	CXCL1	NR_046035.2		n.410-94A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL1	ENST00000395761.4	TSL:1 MANE Select	c.309-94A>G		intron	N/A	ENSP00000379110.3	P09341
	CXCL1	ENST00000951020.1		c.306-94A>G		intron	N/A	ENSP00000621079.1
	CXCL1	ENST00000509101.1	TSL:3	n.*250A>G		downstream_gene	N/A

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

African (AFR) AF: 0.0945 AC: 2954 AN: 31274

American (AMR) AF: 0.447 AC: 18291 AN: 40936

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 12228 AN: 24426

East Asian (EAS) AF: 0.523 AC: 20412 AN: 39026

South Asian (SAS) AF: 0.493 AC: 40478 AN: 82052

European-Finnish (FIN) AF: 0.631 AC: 32688 AN: 51780

Middle Eastern (MID) AF: 0.495 AC: 2745 AN: 5550

European-Non Finnish (NFE) AF: 0.644 AC: 673084 AN: 1045390

Other (OTH) AF: 0.571 AC: 32776 AN: 57436

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

African (AFR) AF: 0.116 AC: 4797 AN: 41502

American (AMR) AF: 0.461 AC: 7037 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1761 AN: 3472

East Asian (EAS) AF: 0.555 AC: 2854 AN: 5146

South Asian (SAS) AF: 0.478 AC: 2305 AN: 4826

European-Finnish (FIN) AF: 0.625 AC: 6592 AN: 10552

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.643 AC: 43722 AN: 67968

Other (OTH) AF: 0.475 AC: 1002 AN: 2110

Alfa AF: 0.595 Hom.: 31237

Bravo AF: 0.437

Asia WGS AF: 0.482 AC: 1675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.71
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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