3-39276422-T-C

Variant names:

• chr3-39276422-T-C
• rs13062158
• NM_001337.4:c.-10+3532A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001337.4(CX3CR1):​c.-10+3532A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,152 control chromosomes in the GnomAD database, including 6,853 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 0.28 (6853 hom., cov: 32)
• Consequence: CX3CR1 NM_001337.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CX3CR1	NM_001337.4	c.-10+3532A>G		intron_variant	Intron 1 of 1	ENST00000399220.3	NP_001328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CX3CR1	ENST00000399220.3	c.-10+3532A>G		intron_variant	Intron 1 of 1	1	NM_001337.4	ENSP00000382166.3

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42807 AN: 152036 Hom.: 6859 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.281 AC: 42814 AN: 152152 Hom.: 6853 Cov.: 32 AF XY: 0.290 AC XY: 21544 AN XY: 74390

African (AFR) AF: 0.162 AC: 6730 AN: 41524

American (AMR) AF: 0.379 AC: 5788 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1111 AN: 3466

East Asian (EAS) AF: 0.672 AC: 3479 AN: 5176

South Asian (SAS) AF: 0.400 AC: 1928 AN: 4826

European-Finnish (FIN) AF: 0.352 AC: 3721 AN: 10576

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19102 AN: 67988

Other (OTH) AF: 0.304 AC: 642 AN: 2114

Alfa AF: 0.286 Hom.: 21427

Bravo AF: 0.280

Asia WGS AF: 0.535 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.2
DANN	Benign	0.66
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13062158; hg19: chr3-39317913;