Genetic Variant CX3CR1:c.*149T>C (chr3-39265293-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001337.4(CX3CR1):c.*149T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 734,944 control chromosomes in the GnomAD database, including 23,413 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4132 hom., cov: 32)

Exomes 𝑓: 0.25 ( 19281 hom. )

Consequence

CX3CR1
NM_001337.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39

Publications

14 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 (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CX3CR1	NM_001337.4 link	c.*149T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000399220.3	NP_001328.1	P49238-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CX3CR1	ENST00000399220.3 link	c.*149T>C	3_prime_UTR_variant	Exon 2 of 2	1	NM_001337.4	ENSP00000382166.3	P49238-1
CX3CR1	ENST00000358309.3 link	c.*149T>C	3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000351059.3	P49238-4
CX3CR1	ENST00000541347.5 link	c.*149T>C	3_prime_UTR_variant	Exon 2 of 2	4		ENSP00000439140.1	P49238-1
CX3CR1	ENST00000542107.5 link	c.*149T>C	3_prime_UTR_variant	Exon 2 of 2	4		ENSP00000444928.1	P49238-1

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33558

AN:

152042

Hom.:

4127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.0256

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.237

GnomAD4 exome

AF:

0.247

AC:

143998

AN:

582784

Hom.:

19281

Cov.:

AF XY:

0.245

AC XY:

73664

AN XY:

301156

show subpopulations

African (AFR)

AF:

0.130

AC:

2039

AN:

15640

American (AMR)

AF:

0.238

AC:

5045

AN:

21220

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

4051

AN:

14378

East Asian (EAS)

AF:

0.0354

AC:

1198

AN:

33852

South Asian (SAS)

AF:

0.131

AC:

5174

AN:

39544

European-Finnish (FIN)

AF:

0.258

AC:

9014

AN:

34946

Middle Eastern (MID)

AF:

0.240

AC:

519

AN:

2162

European-Non Finnish (NFE)

AF:

0.281

AC:

109640

AN:

390760

Other (OTH)

AF:

0.242

AC:

7318

AN:

30282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

5256

10513

15769

21026

26282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1920

3840

5760

7680

9600

<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:

0.221

AC:

33582

AN:

152160

Hom.:

4132

Cov.:

AF XY:

0.217

AC XY:

16125

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.137

AC:

5685

AN:

41538

American (AMR)

AF:

0.226

AC:

3458

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

993

AN:

3472

East Asian (EAS)

AF:

0.0260

AC:

135

AN:

5190

South Asian (SAS)

AF:

0.130

AC:

626

AN:

4828

European-Finnish (FIN)

AF:

0.265

AC:

2802

AN:

10572

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.281

AC:

19115

AN:

67962

Other (OTH)

AF:

0.237

AC:

500

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1318

2637

3955

5274

6592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.263

Hom.:

9670

Bravo

AF:

0.215

Asia WGS

AF:

0.101

AC:

351

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.1

(source)

DANN

Benign

0.86

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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