Genetic Variant CX3CR1:c.-141T>C (chr3-39281174-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_001171171.2(CX3CR1):c.-141T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 1,016,012 control chromosomes in the GnomAD database, including 387,192 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 0.84 ( 54508 hom., cov: 31)

Exomes 𝑓: 0.88 ( 332684 hom. )

Consequence

CX3CR1
NM_001171171.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.532

Publications

9 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171171.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CR1	NM_001171171.2		c.-141T>C		5_prime_UTR	Exon 1 of 2	NP_001164642.1	P49238-1
	CX3CR1	NM_001171174.1		c.87+435T>C		intron	N/A	NP_001164645.1	P49238-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CX3CR1	ENST00000541347.5	TSL:4	c.-141T>C	5_prime_UTR	Exon 1 of 2	ENSP00000439140.1	P49238-1
CX3CR1	ENST00000864857.1		c.-141T>C	5_prime_UTR	Exon 2 of 3	ENSP00000534916.1
CX3CR1	ENST00000963325.1		c.-141T>C	5_prime_UTR	Exon 2 of 3	ENSP00000633384.1

Frequencies

GnomAD3 genomes

AF:

0.844

AC:

128372

AN:

152050

Hom.:

54481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.746

Gnomad AMI

AF:

0.953

Gnomad AMR

AF:

0.866

Gnomad ASJ

AF:

0.858

Gnomad EAS

AF:

0.956

Gnomad SAS

AF:

0.865

Gnomad FIN

AF:

0.886

Gnomad MID

AF:

0.838

Gnomad NFE

AF:

0.881

Gnomad OTH

AF:

0.851

GnomAD4 exome

AF:

0.877

AC:

757777

AN:

863844

Hom.:

332684

Cov.:

AF XY:

0.877

AC XY:

351911

AN XY:

401158

show subpopulations

African (AFR)

AF:

0.739

AC:

11952

AN:

16180

American (AMR)

AF:

0.880

AC:

2768

AN:

3144

Ashkenazi Jewish (ASJ)

AF:

0.857

AC:

4870

AN:

5684

East Asian (EAS)

AF:

0.953

AC:

4073

AN:

4276

South Asian (SAS)

AF:

0.861

AC:

18805

AN:

21848

European-Finnish (FIN)

AF:

0.884

AC:

1354

AN:

1532

Middle Eastern (MID)

AF:

0.855

AC:

1480

AN:

1730

European-Non Finnish (NFE)

AF:

0.881

AC:

687296

AN:

780516

Other (OTH)

AF:

0.870

AC:

25179

AN:

28934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

4548

9096

13643

18191

22739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20062

40124

60186

80248

100310

<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:

0.844

AC:

128452

AN:

152168

Hom.:

54508

Cov.:

AF XY:

0.844

AC XY:

62798

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.746

AC:

30946

AN:

41496

American (AMR)

AF:

0.865

AC:

13245

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.858

AC:

2978

AN:

3470

East Asian (EAS)

AF:

0.956

AC:

4928

AN:

5154

South Asian (SAS)

AF:

0.865

AC:

4169

AN:

4820

European-Finnish (FIN)

AF:

0.886

AC:

9397

AN:

10604

Middle Eastern (MID)

AF:

0.846

AC:

247

AN:

292

European-Non Finnish (NFE)

AF:

0.881

AC:

59882

AN:

68004

Other (OTH)

AF:

0.848

AC:

1791

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1026

2052

3077

4103

5129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.858

Hom.:

7096

Bravo

AF:

0.838

Asia WGS

AF:

0.906

AC:

3150

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

(source)

DANN

Benign

0.40

PhyloP100

-0.53

PromoterAI

-0.025

Neutral

(source)

Mutation Taster

=287/13

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over