ENST00000864857.1:c.-275T>G

Variant names:

• chr3-39281672-A-C
• rs11715522
• ENST00000864857.1:c.-275T>G

Variant summary

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

The ENST00000864857.1(CX3CR1):​c.-275T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,596,944 control chromosomes in the GnomAD database, including 127,985 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 0.36 (10835 hom., cov: 30)
  • Exomes 𝑓: 0.40 (117150 hom.)
• Consequence: CX3CR1 ENST00000864857.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 20 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 (MetaRNN=5.266823E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000864857.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CR1	NM_001171174.1		c.24T>G	p.Phe8Leu	missense	Exon 1 of 2	NP_001164645.1	P49238-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CR1	ENST00000864857.1		c.-275T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000534916.1
	CX3CR1	ENST00000963325.1		c.-271T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000633384.1
	CX3CR1	ENST00000358309.3	TSL:2	c.24T>G	p.Phe8Leu	missense	Exon 1 of 2	ENSP00000351059.3	P49238-4

Frequencies

GnomAD3 genomes AF: 0.363 AC: 54990 AN: 151670 Hom.: 10837 Cov.: 30

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.407

GnomAD2 exomes AF: 0.421 AC: 97940 AN: 232732 AF XY: 0.420

Gnomad AFR exome AF: 0.206

Gnomad AMR exome AF: 0.493

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.678

Gnomad FIN exome AF: 0.441

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.417

GnomAD4 exome AF: 0.397 AC: 573056 AN: 1445156 Hom.: 117150 Cov.: 37 AF XY: 0.398 AC XY: 286174 AN XY: 719292

African (AFR) AF: 0.203 AC: 6790 AN: 33460

American (AMR) AF: 0.492 AC: 21950 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 9085 AN: 26100

East Asian (EAS) AF: 0.689 AC: 27334 AN: 39668

South Asian (SAS) AF: 0.429 AC: 36911 AN: 86106

European-Finnish (FIN) AF: 0.433 AC: 16913 AN: 39084

Middle Eastern (MID) AF: 0.489 AC: 2815 AN: 5762

European-Non Finnish (NFE) AF: 0.384 AC: 426683 AN: 1110140

Other (OTH) AF: 0.408 AC: 24575 AN: 60230

GnomAD4 genome AF: 0.362 AC: 55001 AN: 151788 Hom.: 10835 Cov.: 30 AF XY: 0.369 AC XY: 27398 AN XY: 74170

African (AFR) AF: 0.211 AC: 8744 AN: 41376

American (AMR) AF: 0.462 AC: 7050 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1227 AN: 3472

East Asian (EAS) AF: 0.677 AC: 3478 AN: 5138

South Asian (SAS) AF: 0.440 AC: 2108 AN: 4794

European-Finnish (FIN) AF: 0.449 AC: 4726 AN: 10526

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.387 AC: 26310 AN: 67916

Other (OTH) AF: 0.408 AC: 859 AN: 2104

Alfa AF: 0.391 Hom.: 25268

Bravo AF: 0.358

Asia WGS AF: 0.560 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.51
DANN	Benign	0.66
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0000053	T
MetaSVM	Benign	-0.96	T
PhyloP100		-1.1
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.026
Sift	Benign	0.86	T
PromoterAI		-0.12	Neutral
gMVP		0.31
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11715522;

hg19: chr3-39323163;

COSMIC: COSV64193425;

COSMIC: COSV64193425;