chr3-39265725-A-G

Position:

• chr3-39265725-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001337.4(CX3CR1):​c.785T>C​(p.Phe262Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CX3CR1 NM_001337.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.26

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29043162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CX3CR1	NM_001337.4	c.785T>C	p.Phe262Ser	missense_variant	2/2	ENST00000399220.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CX3CR1	ENST00000399220.3	c.785T>C	p.Phe262Ser	missense_variant	2/2	1	NM_001337.4	P1
CX3CR1	ENST00000358309.3	c.881T>C	p.Phe294Ser	missense_variant	2/2	2
CX3CR1	ENST00000541347.5	c.785T>C	p.Phe262Ser	missense_variant	2/2	4		P1
CX3CR1	ENST00000542107.5	c.785T>C	p.Phe262Ser	missense_variant	2/2	4		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

Functional Genomics, Thrombosis Research Institute, India

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;T;T;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.37	N
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L;.
MutationTaster	Benign	0.82	D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.030	D;D;D;T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		1.0	D;D;D;.
Vest4		0.31
MutPred		0.63		Gain of disorder (P = 0.0204);Gain of disorder (P = 0.0204);Gain of disorder (P = 0.0204);.;
MVP		0.72
MPC		1.3
ClinPred		0.70	D
GERP RS		5.8
Varity_R		0.15
gMVP		0.48

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

Other links and lift over

dbSNP: rs137854870; hg19: chr3-39307216; COSMIC: COSV100843313; COSMIC: COSV100843313;