3-39281174-A-G

Variant summary

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

The NM_001171171.2(CX3CR1):c.-141T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 1,016,012 control chromosomes in the GnomAD database, including 387,192 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 0.84 (54508 hom., cov: 31)
  • Exomes 𝑓: 0.88 (332684 hom.)
• Consequence: CX3CR1 NM_001171171.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CX3CR1	NM_001171171.2	c.-141T>C		5_prime_UTR_variant	1/2
CX3CR1	NM_001171174.1	c.87+435T>C		intron_variant
CX3CR1	XM_047447538.1	c.-10+11618T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CX3CR1	ENST00000412814.1	c.-141T>C		5_prime_UTR_variant	1/2	4
CX3CR1	ENST00000541347.5	c.-141T>C		5_prime_UTR_variant	1/2	4		P1
CX3CR1	ENST00000358309.3	c.87+435T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128372 AN: 152050 Hom.: 54481 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.851

GnomAD4 exome AF: 0.877 AC: 757777 AN: 863844 Hom.: 332684 Cov.: 32 AF XY: 0.877 AC XY: 351911 AN XY: 401158

Gnomad4 AFR exome AF: 0.739

Gnomad4 AMR exome AF: 0.880

Gnomad4 ASJ exome AF: 0.857

Gnomad4 EAS exome AF: 0.953

Gnomad4 SAS exome AF: 0.861

Gnomad4 FIN exome AF: 0.884

Gnomad4 NFE exome AF: 0.881

Gnomad4 OTH exome AF: 0.870

GnomAD4 genome AF: 0.844 AC: 128452 AN: 152168 Hom.: 54508 Cov.: 31 AF XY: 0.844 AC XY: 62798 AN XY: 74374

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.865

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.881

Gnomad4 OTH AF: 0.848

Alfa AF: 0.858 Hom.: 7096

Bravo AF: 0.838

Asia WGS AF: 0.906 AC: 3150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.4
Dann	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs938203; hg19: chr3-39322665;