16-57379748-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002996.6(CX3CL1):c.185C>T(p.Ala62Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00601 in 1,614,242 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0062 ( 43 hom. )

Consequence

CX3CL1
NM_002996.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.970

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]

CX3CL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010627687).

BP6

Variant 16-57379748-C-T is Benign according to our data. Variant chr16-57379748-C-T is described in ClinVar as [Benign]. Clinvar id is 771016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CX3CL1	NM_002996.6 link	c.185C>T	p.Ala62Val	missense_variant	Exon 2 of 3	ENST00000006053.7	NP_002987.1	P78423A0N0N7
CX3CL1	NM_001304392.3 link	c.-64-2282C>T		intron_variant	Intron 1 of 1		NP_001291321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CX3CL1	ENST00000006053.7 link	c.185C>T	p.Ala62Val	missense_variant	Exon 2 of 3	1	NM_002996.6	ENSP00000006053.6	P78423
CX3CL1	ENST00000565912.1 link	c.71C>T	p.Ala24Val	missense_variant	Exon 1 of 2	1		ENSP00000464114.1	J3QRA1
CX3CL1	ENST00000563383.1 link	c.203C>T	p.Ala68Val	missense_variant	Exon 2 of 3	5		ENSP00000456830.1	H3BSR6
CX3CL1	ENST00000564948.1 link	c.71-2282C>T		intron_variant	Intron 1 of 1	3		ENSP00000457996.1	H3BV86

Frequencies

GnomAD3 genomes

AF:

0.00456

AC:

695

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00621

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00802

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00509

AC:

1279

AN:

251454

AF XY:

0.00528

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.00508

Gnomad NFE exome

AF:

0.00880

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00616

AC:

9004

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

4441

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.00110

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.000842

AC:

AN:

26134

Gnomad4 EAS exome

AF:

0.000101

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.00281

AC:

242

AN:

86256

Gnomad4 FIN exome

AF:

0.00537

AC:

287

AN:

53420

Gnomad4 NFE exome

AF:

0.00724

AC:

8047

AN:

1111994

Gnomad4 Remaining exome

AF:

0.00485

AC:

293

AN:

60394

Heterozygous variant carriers

444

887

1331

1774

2218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.00455

AC:

694

AN:

152372

Hom.:

Cov.:

AF XY:

0.00436

AC XY:

325

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000890

AC:

0.000889637

AN:

0.000889637

Gnomad4 AMR

AF:

0.00137

AC:

0.00137201

AN:

0.00137201

Gnomad4 ASJ

AF:

0.00115

AC:

0.00115274

AN:

0.00115274

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00166

AC:

0.00165631

AN:

0.00165631

Gnomad4 FIN

AF:

0.00621

AC:

0.00621001

AN:

0.00621001

Gnomad4 NFE

AF:

0.00801

AC:

0.00801023

AN:

0.00801023

Gnomad4 OTH

AF:

0.00614

AC:

0.00614367

AN:

0.00614367

Heterozygous variant carriers

104

138

173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<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:

0.00686

Hom.:

Bravo

AF:

0.00385

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00674

AC:

ExAC

AF:

0.00577

AC:

701

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00703

EpiControl

AF:

0.00610

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T;.

Eigen

Benign

0.18

Eigen_PC

Benign

-0.0097

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Pathogenic

3.4

M;.;.

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.3

D;D;.

REVEL

Benign

0.25

Sift

Benign

0.069

T;T;.

Sift4G

Benign

0.12

T;T;T

Polyphen

0.94

P;.;.

Vest4

0.47

MVP

0.17

MPC

1.0

ClinPred

0.067

GERP RS

3.2

Varity_R

0.39

gMVP

0.92

Mutation Taster

=80/20

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over