chr16-57382093-G-A

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

Scores

8

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.17
Variant links:
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

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CX3CL1NM_002996.6 linkc.255G>A p.Ala85Ala synonymous_variant Exon 3 of 3 ENST00000006053.7 NP_002987.1 P78423A0N0N7
CX3CL1NM_001304392.3 linkc.-1G>A 5_prime_UTR_variant Exon 2 of 2 NP_001291321.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CX3CL1ENST00000006053.7 linkc.255G>A p.Ala85Ala synonymous_variant Exon 3 of 3 1 NM_002996.6 ENSP00000006053.6 P78423
CX3CL1ENST00000565912.1 linkc.141G>A p.Ala47Ala synonymous_variant Exon 2 of 2 1 ENSP00000464114.1 J3QRA1
CX3CL1ENST00000564948.1 linkc.134G>A p.Arg45Gln missense_variant Exon 2 of 2 3 ENSP00000457996.1 H3BV86
CX3CL1ENST00000563383.1 linkc.273G>A p.Ala91Ala synonymous_variant Exon 3 of 3 5 ENSP00000456830.1 H3BSR6

Frequencies

GnomAD3 genomes
AF:
0.0112
AC:
1710
AN:
152188
Hom.:
38
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0392
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00860
GnomAD2 exomes
AF:
0.00263
AC:
659
AN:
250880
AF XY:
0.00181
show subpopulations
Gnomad AFR exome
AF:
0.0361
Gnomad AMR exome
AF:
0.00145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000328
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.0000705
Gnomad OTH exome
AF:
0.000980
GnomAD4 exome
AF:
0.00107
AC:
1557
AN:
1461430
Hom.:
25
Cov.:
31
AF XY:
0.000931
AC XY:
677
AN XY:
726956
show subpopulations
Gnomad4 AFR exome
AF:
0.0378
AC:
1266
AN:
33474
Gnomad4 AMR exome
AF:
0.00177
AC:
79
AN:
44680
Gnomad4 ASJ exome
AF:
0.00
AC:
0
AN:
26124
Gnomad4 EAS exome
AF:
0.000101
AC:
4
AN:
39690
Gnomad4 SAS exome
AF:
0.0000928
AC:
8
AN:
86204
Gnomad4 FIN exome
AF:
0.00
AC:
0
AN:
53352
Gnomad4 NFE exome
AF:
0.0000549
AC:
61
AN:
1111770
Gnomad4 Remaining exome
AF:
0.00222
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
0
40
80
120
160
200
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0113
AC:
1719
AN:
152306
Hom.:
38
Cov.:
32
AF XY:
0.0109
AC XY:
814
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0393
AC:
0.0393167
AN:
0.0393167
Gnomad4 AMR
AF:
0.00392
AC:
0.00392157
AN:
0.00392157
Gnomad4 ASJ
AF:
0.00
AC:
0
AN:
0
Gnomad4 EAS
AF:
0.000193
AC:
0.000192678
AN:
0.000192678
Gnomad4 SAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 FIN
AF:
0.00
AC:
0
AN:
0
Gnomad4 NFE
AF:
0.0000882
AC:
0.0000882094
AN:
0.0000882094
Gnomad4 OTH
AF:
0.00851
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
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00377
Hom.:
3
Bravo
AF:
0.0122
ESP6500AA
AF:
0.0400
AC:
176
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00337
AC:
409
Asia WGS
AF:
0.000866
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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.79
T
BayesDel_noAF
Benign
-0.87
CADD
Benign
3.7
DANN
Benign
0.60
FATHMM_MKL
Benign
0.0049
N
LIST_S2
Benign
0.50
T
MetaRNN
Benign
0.0031
T
PROVEAN
Benign
-0.020
N
Vest4
0.099
MVP
0.082
GERP RS
-9.8
Mutation Taster
=90/10
polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2229164; hg19: chr16-57416005; API