3-39279727-T-C

Position:

• chr3-39279727-T-C

Variant summary

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

The NM_001337.4(CX3CR1):​c.-10+227A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 152,244 control chromosomes in the GnomAD database, including 58,598 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 0.88 (58598 hom., cov: 32)
• Consequence: CX3CR1 NM_001337.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302

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 = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CX3CR1	NM_001337.4	c.-10+227A>G		intron_variant		ENST00000399220.3	NP_001328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CX3CR1	ENST00000399220.3	c.-10+227A>G		intron_variant		1	NM_001337.4	ENSP00000382166.3

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133384 AN: 152126 Hom.: 58560 Cov.: 32

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.960

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.851

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.877 AC: 133480 AN: 152244 Hom.: 58598 Cov.: 32 AF XY: 0.880 AC XY: 65476 AN XY: 74438

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.961

Gnomad4 FIN AF: 0.894

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.853

Alfa AF: 0.883 Hom.: 10574

Bravo AF: 0.874

Asia WGS AF: 0.966 AC: 3359 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	0.24
DANN	Benign	0.65

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: rs2669845; hg19: chr3-39321218;