16-57379748-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.970

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 -10 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_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CX3CL1	NM_002996.6	c.185C>T	p.Ala62Val	missense_variant	2/3	ENST00000006053.7
CX3CL1	NM_001304392.3	c.-64-2282C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CX3CL1	ENST00000006053.7	c.185C>T	p.Ala62Val	missense_variant	2/3	1	NM_002996.6	P4
CX3CL1	ENST00000565912.1	c.71C>T	p.Ala24Val	missense_variant	1/2	1
CX3CL1	ENST00000563383.1	c.203C>T	p.Ala68Val	missense_variant	2/3	5		A2
CX3CL1	ENST00000564948.1	c.71-2282C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00456 AC: 695 AN: 152254 Hom.: 3 Cov.: 33

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

GnomAD3 exomes AF: 0.00509 AC: 1279 AN: 251454 Hom.: 3 AF XY: 0.00528 AC XY: 718 AN XY: 135890

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 SAS exome AF: 0.00229

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.: 43 Cov.: 31 AF XY: 0.00611 AC XY: 4441 AN XY: 727236

Gnomad4 AFR exome AF: 0.000926

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.000842

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00281

Gnomad4 FIN exome AF: 0.00537

Gnomad4 NFE exome AF: 0.00724

Gnomad4 OTH exome AF: 0.00485

GnomAD4 genome AF: 0.00455 AC: 694 AN: 152372 Hom.: 3 Cov.: 33 AF XY: 0.00436 AC XY: 325 AN XY: 74514

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00621

Gnomad4 NFE AF: 0.00801

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00704 Hom.: 11

Bravo AF: 0.00385

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00675 AC: 26

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00674 AC: 58

ExAC AF: 0.00577 AC: 701

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00703

EpiControl AF: 0.00610

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	18
Dann	Uncertain	1.0
DEOGEN2	Benign	0.38	T;T;.
Eigen	Benign	0.18
Eigen_PC	Benign	-0.0097
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.011	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Pathogenic	3.4	M;.;.
MutationTaster	Benign	0.63	D;D;N;N
PrimateAI	Benign	0.37	T
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	T
GERP RS		3.2
Varity_R		0.39
gMVP		0.92

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: rs62037084; hg19: chr16-57413660;