16-57383222-G-T

Position:

• chr16-57383222-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CX3CL1	NM_002996.6	c.*190G>T		3_prime_UTR_variant	3/3	ENST00000006053.7	NP_002987.1
CX3CL1	NM_001304392.3	c.*190G>T		3_prime_UTR_variant	2/2		NP_001291321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CX3CL1	ENST00000006053.7	c.*190G>T		3_prime_UTR_variant	3/3	1	NM_002996.6	ENSP00000006053.6
CX3CL1	ENST00000565912.1	c.*190G>T		3_prime_UTR_variant	2/2	1		ENSP00000464114.1
CX3CL1	ENST00000563383.1	c.*190G>T		3_prime_UTR_variant	3/3	5		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

Gnomad4 AFR exome AF: 0.721

Gnomad4 AMR exome AF: 0.659

Gnomad4 ASJ exome AF: 0.801

Gnomad4 EAS exome AF: 0.534

Gnomad4 SAS exome AF: 0.583

Gnomad4 FIN exome AF: 0.816

Gnomad4 NFE exome AF: 0.783

Gnomad4 OTH exome AF: 0.761

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

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.770

Alfa AF: 0.776 Hom.: 60375

Bravo AF: 0.744

Asia WGS AF: 0.614 AC: 2135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.014
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4151117; hg19: chr16-57417134;