rs12636547

Positions:

• chr3-39275337-G-C
• chr3-39275337-G-T

Variant summary

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

The NM_001337.4(CX3CR1):​c.-10+4617C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 152,230 control chromosomes in the GnomAD database, including 450 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 0.075 (450 hom., cov: 33)
• Consequence: CX3CR1 NM_001337.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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 (SAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CX3CR1	NM_001337.4	c.-10+4617C>G		intron_variant		ENST00000399220.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CX3CR1	ENST00000399220.3	c.-10+4617C>G		intron_variant		1	NM_001337.4	P1

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11424 AN: 152112 Hom.: 451 Cov.: 33

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0845

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.0441

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0984

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0825

Gnomad OTH AF: 0.0851

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

GnomAD4 genome AF: 0.0751 AC: 11435 AN: 152230 Hom.: 450 Cov.: 33 AF XY: 0.0776 AC XY: 5779 AN XY: 74428

Gnomad4 AFR AF: 0.0531

Gnomad4 AMR AF: 0.0847

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.0442

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0984

Gnomad4 NFE AF: 0.0825

Gnomad4 OTH AF: 0.0880

Alfa AF: 0.0306 Hom.: 19

Bravo AF: 0.0730

Asia WGS AF: 0.0740 AC: 256 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	4.2
DANN	Benign	0.57

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: rs12636547; hg19: chr3-39316828;