rs776223203

Variant names:

• chr3-39265660-T-C
• rs776223203
• NM_001337.4:c.850A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001337.4(CX3CR1):​c.850A>G​(p.Ser284Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CX3CR1 NM_001337.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0620
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34945604).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001337.4. 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_001337.4	MANE Select	c.850A>G	p.Ser284Gly	missense	Exon 2 of 2	NP_001328.1	P49238-1
	CX3CR1	NM_001171174.1		c.946A>G	p.Ser316Gly	missense	Exon 2 of 2	NP_001164645.1	P49238-4
	CX3CR1	NM_001171171.2		c.850A>G	p.Ser284Gly	missense	Exon 2 of 2	NP_001164642.1	P49238-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CR1	ENST00000399220.3	TSL:1 MANE Select	c.850A>G	p.Ser284Gly	missense	Exon 2 of 2	ENSP00000382166.3	P49238-1
	CX3CR1	ENST00000358309.3	TSL:2	c.946A>G	p.Ser316Gly	missense	Exon 2 of 2	ENSP00000351059.3	P49238-4
	CX3CR1	ENST00000541347.5	TSL:4	c.850A>G	p.Ser284Gly	missense	Exon 2 of 2	ENSP00000439140.1	P49238-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249508 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.013
Eigen_PC	Benign	-0.071
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		0.062
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.55	P
Vest4		0.17
MutPred		0.53		Loss of stability (P = 0.1069)
MVP		0.77
MPC		0.26
ClinPred		0.77	D
GERP RS		3.4
Varity_R		0.47
gMVP		0.32
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs776223203; hg19: chr3-39307151;