rs3732379

Positions:

• chr3-39265765-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000399220.3(CX3CR1):​c.745G>A​(p.Val249Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,613,566 control chromosomes in the GnomAD database, including 55,397 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.22 (4122 hom., cov: 32)
  • Exomes 𝑓: 0.26 (51275 hom.)
• Consequence: CX3CR1 ENST00000399220.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003563732).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CX3CR1	NM_001337.4	c.745G>A	p.Val249Ile	missense_variant	2/2	ENST00000399220.3	NP_001328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CX3CR1	ENST00000399220.3	c.745G>A	p.Val249Ile	missense_variant	2/2	1	NM_001337.4	ENSP00000382166	P1
CX3CR1	ENST00000358309.3	c.841G>A	p.Val281Ile	missense_variant	2/2	2		ENSP00000351059
CX3CR1	ENST00000541347.5	c.745G>A	p.Val249Ile	missense_variant	2/2	4		ENSP00000439140	P1
CX3CR1	ENST00000542107.5	c.745G>A	p.Val249Ile	missense_variant	2/2	4		ENSP00000444928	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33463 AN: 151896 Hom.: 4117 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.236

GnomAD3 exomes AF: 0.224 AC: 55820 AN: 249502 Hom.: 7030 AF XY: 0.222 AC XY: 30098 AN XY: 135360

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.0220

Gnomad SAS exome AF: 0.135

Gnomad FIN exome AF: 0.267

Gnomad NFE exome AF: 0.275

Gnomad OTH exome AF: 0.245

GnomAD4 exome AF: 0.259 AC: 378032 AN: 1461552 Hom.: 51275 Cov.: 35 AF XY: 0.255 AC XY: 185610 AN XY: 727110

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.0336

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.220 AC: 33487 AN: 152014 Hom.: 4122 Cov.: 32 AF XY: 0.216 AC XY: 16078 AN XY: 74296

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.0260

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.236

Alfa AF: 0.263 Hom.: 14214

Bravo AF: 0.214

TwinsUK AF: 0.288 AC: 1069

ALSPAC AF: 0.283 AC: 1092

ESP6500AA AF: 0.134 AC: 515

ESP6500EA AF: 0.276 AC: 2281

ExAC AF: 0.221 AC: 26684

Asia WGS AF: 0.101 AC: 352 AN: 3478

EpiCase AF: 0.280

EpiControl AF: 0.279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.059
DANN	Benign	0.36
DEOGEN2	Benign	0.053	T;T;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.72	.;T;.;T
MetaRNN	Benign	0.0036	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.025	N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.40	N;N;N;N
REVEL	Benign	0.046
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.033	B;B;B;.
Vest4		0.045
MPC		0.24
ClinPred		0.0029	T
GERP RS		-2.3
Varity_R		0.027
gMVP		0.071

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: rs3732379; hg19: chr3-39307256; COSMIC: COSV64193563; COSMIC: COSV64193563;