rs3732379

Variant names:

• chr3-39265765-C-T
• rs3732379
• NM_001337.4:c.745G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001337.4(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. 16/21 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 NM_001337.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 248 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: Benign. The variant received -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.

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.745G>A	p.Val249Ile	missense	Exon 2 of 2	NP_001328.1	P49238-1
	CX3CR1	NM_001171174.1		c.841G>A	p.Val281Ile	missense	Exon 2 of 2	NP_001164645.1	P49238-4
	CX3CR1	NM_001171171.2		c.745G>A	p.Val249Ile	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.745G>A	p.Val249Ile	missense	Exon 2 of 2	ENSP00000382166.3	P49238-1
	CX3CR1	ENST00000358309.3	TSL:2	c.841G>A	p.Val281Ile	missense	Exon 2 of 2	ENSP00000351059.3	P49238-4
	CX3CR1	ENST00000541347.5	TSL:4	c.745G>A	p.Val249Ile	missense	Exon 2 of 2	ENSP00000439140.1	P49238-1

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

GnomAD2 exomes AF: 0.224 AC: 55820 AN: 249502 AF XY: 0.222

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 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

African (AFR) AF: 0.132 AC: 4405 AN: 33476

American (AMR) AF: 0.233 AC: 10410 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 7428 AN: 26134

East Asian (EAS) AF: 0.0336 AC: 1334 AN: 39700

South Asian (SAS) AF: 0.133 AC: 11480 AN: 86258

European-Finnish (FIN) AF: 0.259 AC: 13859 AN: 53420

Middle Eastern (MID) AF: 0.240 AC: 1382 AN: 5768

European-Non Finnish (NFE) AF: 0.281 AC: 312911 AN: 1111686

Other (OTH) AF: 0.245 AC: 14823 AN: 60386

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

African (AFR) AF: 0.136 AC: 5654 AN: 41470

American (AMR) AF: 0.226 AC: 3452 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3468

East Asian (EAS) AF: 0.0260 AC: 135 AN: 5190

South Asian (SAS) AF: 0.129 AC: 620 AN: 4816

European-Finnish (FIN) AF: 0.266 AC: 2801 AN: 10534

Middle Eastern (MID) AF: 0.307 AC: 89 AN: 290

European-Non Finnish (NFE) AF: 0.281 AC: 19074 AN: 67960

Other (OTH) AF: 0.236 AC: 498 AN: 2106

Alfa AF: 0.257 Hom.: 26801

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 v4.9

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
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.025	N
PhyloP100		-2.0
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.046
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.033	B
Vest4		0.045
MPC		0.24
ClinPred		0.0029	T
GERP RS		-2.3
Varity_R		0.027
gMVP		0.071
Mutation Taster		=100/0	polymorphism (auto)

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