Variant 3-39265671-G-A 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.839C>T(p.Thr280Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,613,948 control chromosomes in the GnomAD database, including 21,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1435 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19635 hom. )

Consequence

CX3CR1
NM_001337.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89

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=0.0025131404).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 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.839C>T	p.Thr280Met	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.839C>T	p.Thr280Met	missense_variant	2/2	1	NM_001337.4	P1	P49238-1
CX3CR1	ENST00000358309.3 linkuse as main transcript	c.935C>T	p.Thr312Met	missense_variant	2/2	2			P49238-4
CX3CR1	ENST00000541347.5 linkuse as main transcript	c.839C>T	p.Thr280Met	missense_variant	2/2	4		P1	P49238-1
CX3CR1	ENST00000542107.5 linkuse as main transcript	c.839C>T	p.Thr280Met	missense_variant	2/2	4		P1	P49238-1

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18378

AN:

152028

Hom.:

1431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0330

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.0249

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.0892

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.140

AC:

34826

AN:

249502

Hom.:

2881

AF XY:

0.139

AC XY:

18822

AN XY:

135368

show subpopulations

Gnomad AFR exome

AF:

0.0303

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.0217

Gnomad SAS exome

AF:

0.104

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.159

AC:

232796

AN:

1461802

Hom.:

19635

Cov.:

AF XY:

0.158

AC XY:

114842

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0265

Gnomad4 AMR exome

AF:

0.158

Gnomad4 ASJ exome

AF:

0.185

Gnomad4 EAS exome

AF:

0.0335

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.173

Gnomad4 OTH exome

AF:

0.146

GnomAD4 genome

AF:

0.121

AC:

18394

AN:

152146

Hom.:

1435

Cov.:

AF XY:

0.120

AC XY:

8947

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0329

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.178

Gnomad4 EAS

AF:

0.0253

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.167

Gnomad4 NFE

AF:

0.171

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.158

Hom.:

5091

Bravo

AF:

0.114

TwinsUK

AF:

0.178

AC:

661

ALSPAC

AF:

0.178

AC:

685

ESP6500AA

AF:

0.0322

AC:

126

ESP6500EA

AF:

0.172

AC:

1432

ExAC

AF:

0.136

AC:

16453

Asia WGS

AF:

0.0810

AC:

279

AN:

3478

EpiCase

AF:

0.162

EpiControl

AF:

0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;T;T;.

Eigen

Benign

0.026

Eigen_PC

Benign

0.0021

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.90

.;D;.;D

MetaRNN

Benign

0.0025

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M;M;.

MutationTaster

Benign

0.99

P;P;P;P

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.9

D;D;D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.0090

D;D;D;T

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

0.77

P;P;P;.

Vest4

0.27

MPC

0.46

ClinPred

0.028

GERP RS

4.0

Varity_R

0.092

gMVP

0.30

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