NM_001171174.1:c.24T>A

Variant names:

• chr3-39281672-A-T
• rs11715522
• NM_001171174.1:c.24T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001171174.1(CX3CR1):​c.24T>A​(p.Phe8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CX3CR1 NM_001171174.1 missense
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06783414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CX3CR1	NM_001171174.1	c.24T>A	p.Phe8Leu	missense_variant	Exon 1 of 2		NP_001164645.1
CX3CR1	XM_047447538.1	c.-10+11120T>A		intron_variant	Intron 1 of 1		XP_047303494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CX3CR1	ENST00000358309.3	c.24T>A	p.Phe8Leu	missense_variant	Exon 1 of 2	2		ENSP00000351059.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1446464 Hom.: 0 Cov.: 37 AF XY: 0.00000278 AC XY: 2 AN XY: 719856

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111324

Other (OTH) AF: 0.00 AC: 0 AN: 60264

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.43
DANN	Benign	0.71
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.97	T
PhyloP100		-1.1
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.033
Sift	Benign	0.86	T
Vest4		0.041
MutPred		0.28		Gain of ubiquitination at K9 (P = 0.0396);
MVP		0.45
MPC		0.32
ClinPred		0.025	T
GERP RS		-2.4
PromoterAI		-0.090	Neutral
gMVP		0.31
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs11715522; hg19: chr3-39323163;