chr3-39265939-G-T

Variant names:

• chr3-39265939-G-T
• rs200607201
• NM_001337.4:c.571C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001337.4(CX3CR1):​c.571C>A​(p.Arg191Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CX3CR1 NM_001337.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076728106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CX3CR1	NM_001337.4	c.571C>A	p.Arg191Ser	missense_variant	Exon 2 of 2	ENST00000399220.3	NP_001328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CX3CR1	ENST00000399220.3	c.571C>A	p.Arg191Ser	missense_variant	Exon 2 of 2	1	NM_001337.4	ENSP00000382166.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249540 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135384

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.078	T;T;T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.85	.;T;.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.077	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N;N;N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.39	N;N;N;N
REVEL	Benign	0.054
Sift	Benign	0.69	T;T;T;T
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.039	B;B;B;.
Vest4		0.11
MutPred		0.39		Loss of catalytic residue at R191 (P = 0.1);Loss of catalytic residue at R191 (P = 0.1);Loss of catalytic residue at R191 (P = 0.1);.;
MVP		0.44
MPC		0.37
ClinPred		0.066	T
GERP RS		3.8
Varity_R		0.23
gMVP		0.54

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: rs200607201; hg19: chr3-39307430;