16-57382093-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_002996.6(CX3CL1):c.255G>A(p.Ala85=) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

ACMG classification

Verdict is Benign. Variant got -15 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_single_submitter, 1 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 38 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CX3CL1	NM_002996.6	c.255G>A	p.Ala85=	synonymous_variant	3/3	ENST00000006053.7
CX3CL1	NM_001304392.3	c.-1G>A		5_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CX3CL1	ENST00000006053.7	c.255G>A	p.Ala85=	synonymous_variant	3/3	1	NM_002996.6	P4
CX3CL1	ENST00000565912.1	c.141G>A	p.Ala47=	synonymous_variant	2/2	1
CX3CL1	ENST00000564948.1	c.134G>A	p.Arg45Gln	missense_variant	2/2	3
CX3CL1	ENST00000563383.1	c.273G>A	p.Ala91=	synonymous_variant	3/3	5		A2

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1710 AN: 152188 Hom.: 38 Cov.: 32

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

GnomAD3 exomes AF: 0.00263 AC: 659 AN: 250880 Hom.: 11 AF XY: 0.00181 AC XY: 246 AN XY: 135644

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 SAS exome AF: 0.0000654

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

Gnomad4 AFR exome AF: 0.0378

Gnomad4 AMR exome AF: 0.00177

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000549

Gnomad4 OTH exome AF: 0.00222

GnomAD4 genome AF: 0.0113 AC: 1719 AN: 152306 Hom.: 38 Cov.: 32 AF XY: 0.0109 AC XY: 814 AN XY: 74468

Gnomad4 AFR AF: 0.0393

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00378 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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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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
MutationTaster	Benign	1.0	N;N;N;N
PROVEAN	Benign	-0.020	N
Vest4		0.099
MVP		0.082
GERP RS		-9.8

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: rs2229164; hg19: chr16-57416005;