rs150319988

Variant names:

• chr3-39265558-G-A
• rs150319988
• NM_001337.4:c.952C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-39265558-G-A
• chr3-39265558-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001337.4(CX3CR1):​c.952C>T​(p.Arg318Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,614,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: CX3CR1 NM_001337.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.067084074).

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.952C>T	p.Arg318Cys	missense	Exon 2 of 2	NP_001328.1	P49238-1
	CX3CR1	NM_001171174.1		c.1048C>T	p.Arg350Cys	missense	Exon 2 of 2	NP_001164645.1	P49238-4
	CX3CR1	NM_001171171.2		c.952C>T	p.Arg318Cys	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.952C>T	p.Arg318Cys	missense	Exon 2 of 2	ENSP00000382166.3	P49238-1
	CX3CR1	ENST00000358309.3	TSL:2	c.1048C>T	p.Arg350Cys	missense	Exon 2 of 2	ENSP00000351059.3	P49238-4
	CX3CR1	ENST00000541347.5	TSL:4	c.952C>T	p.Arg318Cys	missense	Exon 2 of 2	ENSP00000439140.1	P49238-1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152142 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000148 AC: 37 AN: 249538 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.000660

GnomAD4 exome AF: 0.000105 AC: 154 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.0000935 AC XY: 68 AN XY: 727248

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.000514 AC: 23 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: 0.0000116 AC: 1 AN: 86258

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

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000103 AC: 114 AN: 1112012

Other (OTH) AF: 0.000215 AC: 13 AN: 60396

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152260 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74438

African (AFR) AF: 0.0000241 AC: 1 AN: 41544

American (AMR) AF: 0.000262 AC: 4 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68024

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000124 Hom.: 0

Bravo AF: 0.0000831

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000240 AC: 2

ExAC AF: 0.0000910 AC: 11

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

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	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.11	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.3
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.11
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.017	D
Polyphen		0.99	D
Vest4		0.090
MVP		0.66
MPC		0.37
ClinPred		0.12	T
GERP RS		3.9
Varity_R		0.12
gMVP		0.38
Mutation Taster		=98/2	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: rs150319988; hg19: chr3-39307049;