rs1050592

Positions:

• chr3-39265293-A-G

Variant summary

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

The NM_001337.4(CX3CR1):​c.*149T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 734,944 control chromosomes in the GnomAD database, including 23,413 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4132 hom., cov: 32)
  • Exomes 𝑓: 0.25 (19281 hom.)
• Consequence: CX3CR1 NM_001337.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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 (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CX3CR1	NM_001337.4	c.*149T>C		3_prime_UTR_variant	2/2	ENST00000399220.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CX3CR1	ENST00000399220.3	c.*149T>C		3_prime_UTR_variant	2/2	1	NM_001337.4	P1
CX3CR1	ENST00000358309.3	c.*149T>C		3_prime_UTR_variant	2/2	2
CX3CR1	ENST00000541347.5	c.*149T>C		3_prime_UTR_variant	2/2	4		P1
CX3CR1	ENST00000542107.5	c.*149T>C		3_prime_UTR_variant	2/2	4		P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33558 AN: 152042 Hom.: 4127 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.247 AC: 143998 AN: 582784 Hom.: 19281 Cov.: 8 AF XY: 0.245 AC XY: 73664 AN XY: 301156

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.0354

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.221 AC: 33582 AN: 152160 Hom.: 4132 Cov.: 32 AF XY: 0.217 AC XY: 16125 AN XY: 74374

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.0260

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.237

Alfa AF: 0.268 Hom.: 7303

Bravo AF: 0.215

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.1
DANN	Benign	0.86

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: rs1050592; hg19: chr3-39306784;