dbSNP rs751730918: CX3CL1:p.Leu169Pro (chr16-57382344-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002996.6(CX3CL1):c.506T>C(p.Leu169Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000999 in 1,601,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CX3CL1
NM_002996.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.274

Publications

0 publications found

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049847245).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CL1	NM_002996.6	MANE Select	c.506T>C	p.Leu169Pro	missense	Exon 3 of 3	NP_002987.1	P78423
	CX3CL1	NM_001304392.3		c.251T>C	p.Leu84Pro	missense	Exon 2 of 2	NP_001291321.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CX3CL1	ENST00000006053.7	TSL:1 MANE Select	c.506T>C	p.Leu169Pro	missense	Exon 3 of 3	ENSP00000006053.6	P78423
CX3CL1	ENST00000565912.1	TSL:1	c.392T>C	p.Leu131Pro	missense	Exon 2 of 2	ENSP00000464114.1	J3QRA1
CX3CL1	ENST00000563383.1	TSL:5	c.524T>C	p.Leu175Pro	missense	Exon 3 of 3	ENSP00000456830.1	H3BSR6

Frequencies

GnomAD3 genomes

AF:

0.0000660

AC:

AN:

151434

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000826

AC:

AN:

242012

AF XY:

0.0000152

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000414

AC:

AN:

1450286

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

721182

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33336

American (AMR)

AF:

0.00

AC:

AN:

43938

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25950

East Asian (EAS)

AF:

0.00

AC:

AN:

39436

South Asian (SAS)

AF:

0.00

AC:

AN:

84994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107110

Other (OTH)

AF:

0.00

AC:

AN:

59936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000660

AC:

AN:

151434

Hom.:

Cov.:

AF XY:

0.0000947

AC XY:

AN XY:

73922

show subpopulations

African (AFR)

AF:

0.000243

AC:

AN:

41104

American (AMR)

AF:

0.00

AC:

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67852

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.5

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.16

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00072

LIST_S2

Benign

0.24

M_CAP

Benign

0.0029

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

PhyloP100

-0.27

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.56

REVEL

Benign

0.045

Sift

Benign

0.054

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.053

MVP

0.043

MPC

0.48

ClinPred

0.031

GERP RS

1.1

Varity_R

0.17

gMVP

0.12

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over