Variant 3-39265765-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001337.4(CX3CR1):c.745G>A(p.Val249Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,613,566 control chromosomes in the GnomAD database, including 55,397 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: 𝑓 0.22 ( 4122 hom., cov: 32)

Exomes 𝑓: 0.26 ( 51275 hom. )

Consequence

CX3CR1
NM_001337.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97

Variant links:

Genes affected

CX3CR1 (HGNC:2558): (C-X3-C motif chemokine receptor 1) Fractalkine is a transmembrane protein and chemokine involved in the adhesion and migration of leukocytes. The protein encoded by this gene is a receptor for fractalkine. The encoded protein also is a coreceptor for HIV-1, and some variations in this gene lead to increased susceptibility to HIV-1 infection and rapid progression to AIDS. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

CX3CR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003563732).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CX3CR1	NM_001337.4 linkuse as main transcript	c.745G>A	p.Val249Ile	missense_variant	2/2	ENST00000399220.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CX3CR1	ENST00000399220.3 linkuse as main transcript	c.745G>A	p.Val249Ile	missense_variant	2/2	1	NM_001337.4	P1	P49238-1
CX3CR1	ENST00000358309.3 linkuse as main transcript	c.841G>A	p.Val281Ile	missense_variant	2/2	2			P49238-4
CX3CR1	ENST00000541347.5 linkuse as main transcript	c.745G>A	p.Val249Ile	missense_variant	2/2	4		P1	P49238-1
CX3CR1	ENST00000542107.5 linkuse as main transcript	c.745G>A	p.Val249Ile	missense_variant	2/2	4		P1	P49238-1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33463

AN:

151896

Hom.:

4117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.0256

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.236

GnomAD3 exomes

AF:

0.224

AC:

55820

AN:

249502

Hom.:

7030

AF XY:

0.222

AC XY:

30098

AN XY:

135360

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.231

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.0220

Gnomad SAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.275

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.259

AC:

378032

AN:

1461552

Hom.:

51275

Cov.:

AF XY:

0.255

AC XY:

185610

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.0336

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.259

Gnomad4 NFE exome

AF:

0.281

Gnomad4 OTH exome

AF:

0.245

GnomAD4 genome

AF:

0.220

AC:

33487

AN:

152014

Hom.:

4122

Cov.:

AF XY:

0.216

AC XY:

16078

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.226

Gnomad4 ASJ

AF:

0.285

Gnomad4 EAS

AF:

0.0260

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.281

Gnomad4 OTH

AF:

0.236

Alfa

AF:

0.263

Hom.:

14214

Bravo

AF:

0.214

TwinsUK

AF:

0.288

AC:

1069

ALSPAC

AF:

0.283

AC:

1092

ESP6500AA

AF:

0.134

AC:

515

ESP6500EA

AF:

0.276

AC:

2281

ExAC

AF:

0.221

AC:

26684

Asia WGS

AF:

0.101

AC:

352

AN:

3478

EpiCase

AF:

0.280

EpiControl

AF:

0.279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.059

DANN

Benign

0.36

DEOGEN2

Benign

0.053

T;T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.72

.;T;.;T

MetaRNN

Benign

0.0036

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.025

N;N;N;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

0.40

N;N;N;N

REVEL

Benign

0.046

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.033

B;B;B;.

Vest4

0.045

MPC

0.24

ClinPred

0.0029

GERP RS

-2.3

Varity_R

0.027

gMVP

0.071

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over