Variant 3-39265738-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001337.4(CX3CR1):c.772C>T(p.Leu258Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,614,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

CX3CR1
NM_001337.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.18

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03567326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CX3CR1	NM_001337.4 linkuse as main transcript	c.772C>T	p.Leu258Phe	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.772C>T	p.Leu258Phe	missense_variant	2/2	1	NM_001337.4	P1	P49238-1
CX3CR1	ENST00000358309.3 linkuse as main transcript	c.868C>T	p.Leu290Phe	missense_variant	2/2	2			P49238-4
CX3CR1	ENST00000541347.5 linkuse as main transcript	c.772C>T	p.Leu258Phe	missense_variant	2/2	4		P1	P49238-1
CX3CR1	ENST00000542107.5 linkuse as main transcript	c.772C>T	p.Leu258Phe	missense_variant	2/2	4		P1	P49238-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000962

AC:

AN:

249492

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135352

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00111

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000745

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

The c.772C>T (p.L258F) alteration is located in exon 2 (coding exon 1) of the CX3CR1 gene. This alteration results from a C to T substitution at nucleotide position 772, causing the leucine (L) at amino acid position 258 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.3

DANN

Uncertain

0.98

DEOGEN2

Benign

0.062

T;T;T;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.65

.;T;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.036

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.13

N;N;N;N

REVEL

Benign

0.070

Sift

Benign

0.12

T;T;T;T

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.0070

B;B;B;.

Vest4

0.030

MutPred

0.46

Gain of catalytic residue at L258 (P = 0.0187);Gain of catalytic residue at L258 (P = 0.0187);Gain of catalytic residue at L258 (P = 0.0187);.;

MVP

0.63

MPC

0.30

ClinPred

0.015

GERP RS

-0.031

Varity_R

0.091

gMVP

0.12

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over