16-57383222-G-T

Variant names:

• chr16-57383222-G-T
• rs4151117
• NM_002996.6:c.*190G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002996.6(CX3CL1):​c.*190G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 449,042 control chromosomes in the GnomAD database, including 129,584 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 0.75 (43153 hom., cov: 30)
  • Exomes 𝑓: 0.76 (86431 hom.)
• Consequence: CX3CL1 NM_002996.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00
• Publications: 22 publications found

Genes affected

CX3CL1 (HGNC:10647): (C-X3-C motif chemokine ligand 1) This gene belongs to the CX3C subgroup of chemokines, characterized by the number of amino acids located between the conserved cysteine residues. This is the only member of the CX3C subgroup, which contains three amino acids between cysteine residues, resulting in a Cys-X-X-X-Cys configuration. The encoded protein contains an extended mucin-like stalk with a chemokine domain on top, and exists in both a membrane-anchored form where it acts as a binding molecule, or, in soluble form, as a chemotactic cytokine. The mature form of this protein can be cleaved at the cell surface, yielding different soluble forms that can interact with the G-protein coupled receptor, C-X3-C motif chemokine receptor 1 gene product. This gene plays a role in a wide range of diseases, including cancer, vasculitis, neuropathies, atherosclerosis, inflammatory diseases, and in human immunodeficiency virus infections. [provided by RefSeq, Sep 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002996.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CL1	NM_002996.6	MANE Select	c.*190G>T		3_prime_UTR	Exon 3 of 3	NP_002987.1
	CX3CL1	NM_001304392.3		c.*190G>T		3_prime_UTR	Exon 2 of 2	NP_001291321.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CL1	ENST00000006053.7	TSL:1 MANE Select	c.*190G>T		3_prime_UTR	Exon 3 of 3	ENSP00000006053.6
	CX3CL1	ENST00000565912.1	TSL:1	c.*190G>T		3_prime_UTR	Exon 2 of 2	ENSP00000464114.1
	CX3CL1	ENST00000563383.1	TSL:5	c.*190G>T		3_prime_UTR	Exon 3 of 3	ENSP00000456830.1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114024 AN: 151816 Hom.: 43129 Cov.: 30

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.768

GnomAD4 exome AF: 0.758 AC: 225125 AN: 297106 Hom.: 86431 Cov.: 5 AF XY: 0.760 AC XY: 113869 AN XY: 149906

African (AFR) AF: 0.721 AC: 5910 AN: 8196

American (AMR) AF: 0.659 AC: 5009 AN: 7606

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 7656 AN: 9564

East Asian (EAS) AF: 0.534 AC: 12360 AN: 23130

South Asian (SAS) AF: 0.583 AC: 2269 AN: 3894

European-Finnish (FIN) AF: 0.816 AC: 18112 AN: 22190

Middle Eastern (MID) AF: 0.784 AC: 1116 AN: 1424

European-Non Finnish (NFE) AF: 0.783 AC: 159056 AN: 203188

Other (OTH) AF: 0.761 AC: 13637 AN: 17914

GnomAD4 genome AF: 0.751 AC: 114103 AN: 151936 Hom.: 43153 Cov.: 30 AF XY: 0.746 AC XY: 55413 AN XY: 74256

African (AFR) AF: 0.722 AC: 29894 AN: 41422

American (AMR) AF: 0.698 AC: 10652 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2774 AN: 3464

East Asian (EAS) AF: 0.637 AC: 3276 AN: 5146

South Asian (SAS) AF: 0.570 AC: 2742 AN: 4808

European-Finnish (FIN) AF: 0.820 AC: 8683 AN: 10586

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53557 AN: 67930

Other (OTH) AF: 0.770 AC: 1627 AN: 2112

Alfa AF: 0.773 Hom.: 81087

Bravo AF: 0.744

Asia WGS AF: 0.614 AC: 2135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.014
DANN	Benign	0.40
PhyloP100		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4151117; hg19: chr16-57417134;