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

Publications

20 publications found

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

African (AFR)

AF:

0.203

AC:

6790

AN:

33460

American (AMR)

AF:

0.492

AC:

21950

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

9085

AN:

26100

East Asian (EAS)

AF:

0.689

AC:

27334

AN:

39668

South Asian (SAS)

AF:

0.429

AC:

36911

AN:

86106

European-Finnish (FIN)

AF:

0.433

AC:

16913

AN:

39084

Middle Eastern (MID)

AF:

0.489

AC:

2815

AN:

5762

European-Non Finnish (NFE)

AF:

0.384

AC:

426683

AN:

1110140

Other (OTH)

AF:

0.408

AC:

24575

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

16622

33244

49866

66488

83110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

African (AFR)

AF:

0.211

AC:

8744

AN:

41376

American (AMR)

AF:

0.462

AC:

7050

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

1227

AN:

3472

East Asian (EAS)

AF:

0.677

AC:

3478

AN:

5138

South Asian (SAS)

AF:

0.440

AC:

2108

AN:

4794

European-Finnish (FIN)

AF:

0.449

AC:

4726

AN:

10526

Middle Eastern (MID)

AF:

0.442

AC:

129

AN:

292

European-Non Finnish (NFE)

AF:

0.387

AC:

26310

AN:

67916

Other (OTH)

AF:

0.408

AC:

859

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1682

3364

5047

6729

8411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.51

(source)

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

PhyloP100

-1.1

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

PromoterAI

-0.12

Neutral

(source)

gMVP

0.31

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over