chr3-39281672-A-C

Position:

• chr3-39281672-A-C

Variant summary

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

The NM_001171174.1(CX3CR1):​c.24T>G​(p.Phe8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,596,944 control chromosomes in the GnomAD database, including 127,985 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10835 hom., cov: 30)
  • Exomes 𝑓: 0.40 (117150 hom.)
• Consequence: CX3CR1 NM_001171174.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=5.266823E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CX3CR1	NM_001171174.1	c.24T>G	p.Phe8Leu	missense_variant	1/2		NP_001164645.1
CX3CR1	XM_047447538.1	c.-10+11120T>G		intron_variant			XP_047303494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CX3CR1	ENST00000358309.3	c.24T>G	p.Phe8Leu	missense_variant	1/2	2		ENSP00000351059.3

Frequencies

GnomAD3 genomes AF: 0.363 AC: 54990 AN: 151670 Hom.: 10837 Cov.: 30

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.407

GnomAD3 exomes AF: 0.421 AC: 97940 AN: 232732 Hom.: 21828 AF XY: 0.420 AC XY: 53540 AN XY: 127374

Gnomad AFR exome AF: 0.206

Gnomad AMR exome AF: 0.493

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.678

Gnomad SAS exome AF: 0.435

Gnomad FIN exome AF: 0.441

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.417

GnomAD4 exome AF: 0.397 AC: 573056 AN: 1445156 Hom.: 117150 Cov.: 37 AF XY: 0.398 AC XY: 286174 AN XY: 719292

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.492

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.689

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.433

Gnomad4 NFE exome AF: 0.384

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.362 AC: 55001 AN: 151788 Hom.: 10835 Cov.: 30 AF XY: 0.369 AC XY: 27398 AN XY: 74170

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.408

Alfa AF: 0.392 Hom.: 18105

Bravo AF: 0.358

TwinsUK AF: 0.375 AC: 1389

ALSPAC AF: 0.372 AC: 1435

ESP6500AA AF: 0.198 AC: 622

ESP6500EA AF: 0.386 AC: 2763

ExAC AF: 0.410 AC: 48613

Asia WGS AF: 0.560 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.51
DANN	Benign	0.66
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0000053	T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.026
Sift	Benign	0.86	T
Vest4		0.041
MutPred		0.28		Gain of ubiquitination at K9 (P = 0.0396);
MPC		0.32
ClinPred		0.0019	T
GERP RS		-2.4
gMVP		0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11715522; hg19: chr3-39323163; COSMIC: COSV64193425; COSMIC: COSV64193425;