dbSNP rs11715522: CX3CR1:p.Phe8Leu (chr3-39281672-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001171174.1(CX3CR1):c.24T>G(p.Phe8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,596,944 control chromosomes in the GnomAD database, including 127,985 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 10835 hom., cov: 30)

Exomes 𝑓: 0.40 ( 117150 hom. )

Consequence

CX3CR1
NM_001171174.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.266823E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CX3CR1	NM_001171174.1 link	c.24T>G	p.Phe8Leu	missense_variant	Exon 1 of 2		NP_001164645.1	P49238-4
CX3CR1	XM_047447538.1 link	c.-10+11120T>G		intron_variant	Intron 1 of 1		XP_047303494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CX3CR1	ENST00000358309.3 link	c.24T>G	p.Phe8Leu	missense_variant	Exon 1 of 2	2		ENSP00000351059.3		P49238-4

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

54990

AN:

151670

Hom.:

10837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.462

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.677

Gnomad SAS

AF:

0.441

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.407

GnomAD2 exomes

AF:

0.421

AC:

97940

AN:

232732

AF XY:

0.420

show subpopulations

Gnomad AFR exome

AF:

0.206

Gnomad AMR exome

AF:

0.493

Gnomad ASJ exome

AF:

0.348

Gnomad EAS exome

AF:

0.678

Gnomad FIN exome

AF:

0.441

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.397

AC:

573056

AN:

1445156

Hom.:

117150

Cov.:

AF XY:

0.398

AC XY:

286174

AN XY:

719292

show subpopulations

Gnomad4 AFR exome

AF:

0.203

AC:

6790

AN:

33460

Gnomad4 AMR exome

AF:

0.492

AC:

21950

AN:

44606

Gnomad4 ASJ exome

AF:

0.348

AC:

9085

AN:

26100

Gnomad4 EAS exome

AF:

0.689

AC:

27334

AN:

39668

Gnomad4 SAS exome

AF:

0.429

AC:

36911

AN:

86106

Gnomad4 FIN exome

AF:

0.433

AC:

16913

AN:

39084

Gnomad4 NFE exome

AF:

0.384

AC:

426683

AN:

1110140

Gnomad4 Remaining exome

AF:

0.408

AC:

24575

AN:

60230

Heterozygous variant carriers

16622

33244

49866

66488

83110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

13540

27080

40620

54160

67700

<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:

0.362

AC:

55001

AN:

151788

Hom.:

10835

Cov.:

AF XY:

0.369

AC XY:

27398

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.211

AC:

0.21133

AN:

0.21133

Gnomad4 AMR

AF:

0.462

AC:

0.461871

AN:

0.461871

Gnomad4 ASJ

AF:

0.353

AC:

0.353399

AN:

0.353399

Gnomad4 EAS

AF:

0.677

AC:

0.676917

AN:

0.676917

Gnomad4 SAS

AF:

0.440

AC:

0.439716

AN:

0.439716

Gnomad4 FIN

AF:

0.449

AC:

0.448983

AN:

0.448983

Gnomad4 NFE

AF:

0.387

AC:

0.38739

AN:

0.38739

Gnomad4 OTH

AF:

0.408

AC:

0.40827

AN:

0.40827

Heterozygous variant carriers

1682

3364

5047

6729

8411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.391

Hom.:

25268

Bravo

AF:

0.358

TwinsUK

AF:

0.375

AC:

1389

ALSPAC

AF:

0.372

AC:

1435

ESP6500AA

AF:

0.198

AC:

622

ESP6500EA

AF:

0.386

AC:

2763

ExAC

AF:

0.410

AC:

48613

Asia WGS

AF:

0.560

AC:

1947

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.51

DANN

Benign

0.66

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0000053

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.040

REVEL

Benign

0.026

Sift

Benign

0.86

Vest4

0.041

MutPred

0.28

Gain of ubiquitination at K9 (P = 0.0396);

MPC

0.32

ClinPred

0.0019

GERP RS

-2.4

gMVP

0.31

Mutation Taster

=99/1

polymorphism (auto)

Splicing

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