chr16-57382093-G-A
Variant names:
Variant summary
Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_002996.6(CX3CL1):c.255G>A(p.Ala85Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,613,736 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.011 ( 38 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 25 hom. )
Consequence
CX3CL1
NM_002996.6 synonymous
NM_002996.6 synonymous
Scores
8
Clinical Significance
Conservation
PhyloP100: -1.17
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]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -21 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.003140062).
BP6
Variant 16-57382093-G-A is Benign according to our data. Variant chr16-57382093-G-A is described in ClinVar as [Benign]. Clinvar id is 716483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.17 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0113 (1719/152306) while in subpopulation AFR AF = 0.0393 (1634/41560). AF 95% confidence interval is 0.0377. There are 38 homozygotes in GnomAd4. There are 814 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
BS2
High Homozygotes in GnomAd4 at 38 gene
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CX3CL1 | ENST00000006053.7 | c.255G>A | p.Ala85Ala | synonymous_variant | Exon 3 of 3 | 1 | NM_002996.6 | ENSP00000006053.6 | ||
CX3CL1 | ENST00000565912.1 | c.141G>A | p.Ala47Ala | synonymous_variant | Exon 2 of 2 | 1 | ENSP00000464114.1 | |||
CX3CL1 | ENST00000564948.1 | c.134G>A | p.Arg45Gln | missense_variant | Exon 2 of 2 | 3 | ENSP00000457996.1 | |||
CX3CL1 | ENST00000563383.1 | c.273G>A | p.Ala91Ala | synonymous_variant | Exon 3 of 3 | 5 | ENSP00000456830.1 |
Frequencies
GnomAD3 genomes AF: 0.0112 AC: 1710AN: 152188Hom.: 38 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1710
AN:
152188
Hom.:
Cov.:
32
Gnomad AFR
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GnomAD2 exomes AF: 0.00263 AC: 659AN: 250880 AF XY: 0.00181 show subpopulations
GnomAD2 exomes
AF:
AC:
659
AN:
250880
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.00107 AC: 1557AN: 1461430Hom.: 25 Cov.: 31 AF XY: 0.000931 AC XY: 677AN XY: 726956 show subpopulations
GnomAD4 exome
AF:
AC:
1557
AN:
1461430
Hom.:
Cov.:
31
AF XY:
AC XY:
677
AN XY:
726956
Gnomad4 AFR exome
AF:
AC:
1266
AN:
33474
Gnomad4 AMR exome
AF:
AC:
79
AN:
44680
Gnomad4 ASJ exome
AF:
AC:
0
AN:
26124
Gnomad4 EAS exome
AF:
AC:
4
AN:
39690
Gnomad4 SAS exome
AF:
AC:
8
AN:
86204
Gnomad4 FIN exome
AF:
AC:
0
AN:
53352
Gnomad4 NFE exome
AF:
AC:
61
AN:
1111770
Gnomad4 Remaining exome
AF:
AC:
134
AN:
60370
Heterozygous variant carriers
0
89
179
268
358
447
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
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Age
GnomAD4 genome AF: 0.0113 AC: 1719AN: 152306Hom.: 38 Cov.: 32 AF XY: 0.0109 AC XY: 814AN XY: 74468 show subpopulations
GnomAD4 genome
AF:
AC:
1719
AN:
152306
Hom.:
Cov.:
32
AF XY:
AC XY:
814
AN XY:
74468
Gnomad4 AFR
AF:
AC:
0.0393167
AN:
0.0393167
Gnomad4 AMR
AF:
AC:
0.00392157
AN:
0.00392157
Gnomad4 ASJ
AF:
AC:
0
AN:
0
Gnomad4 EAS
AF:
AC:
0.000192678
AN:
0.000192678
Gnomad4 SAS
AF:
AC:
0
AN:
0
Gnomad4 FIN
AF:
AC:
0
AN:
0
Gnomad4 NFE
AF:
AC:
0.0000882094
AN:
0.0000882094
Gnomad4 OTH
AF:
AC:
0.00851466
AN:
0.00851466
Heterozygous variant carriers
0
79
158
237
316
395
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
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Age
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
176
ESP6500EA
AF:
AC:
0
ExAC
AF:
AC:
409
Asia WGS
AF:
AC:
3
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
PROVEAN
Benign
N
Vest4
MVP
GERP RS
Mutation Taster
=90/10
polymorphism
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at