NM_001337.4:c.571C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001337.4(CX3CR1):​c.571C>T​(p.Arg191Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,614,172 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (7 hom.)
• Consequence: CX3CR1 NM_001337.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.208
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0067015886).
• BP6: Variant 3-39265939-G-A is Benign according to our data. Variant chr3-39265939-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3058556.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001337.4. 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_001337.4	MANE Select	c.571C>T	p.Arg191Cys	missense	Exon 2 of 2	NP_001328.1	P49238-1
	CX3CR1	NM_001171174.1		c.667C>T	p.Arg223Cys	missense	Exon 2 of 2	NP_001164645.1	P49238-4
	CX3CR1	NM_001171171.2		c.571C>T	p.Arg191Cys	missense	Exon 2 of 2	NP_001164642.1	P49238-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CX3CR1	ENST00000399220.3	TSL:1 MANE Select	c.571C>T	p.Arg191Cys	missense	Exon 2 of 2	ENSP00000382166.3	P49238-1
	CX3CR1	ENST00000358309.3	TSL:2	c.667C>T	p.Arg223Cys	missense	Exon 2 of 2	ENSP00000351059.3	P49238-4
	CX3CR1	ENST00000541347.5	TSL:4	c.571C>T	p.Arg191Cys	missense	Exon 2 of 2	ENSP00000439140.1	P49238-1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000521 AC: 130 AN: 249540 AF XY: 0.000687

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000244 AC: 357 AN: 1461884 Hom.: 7 Cov.: 33 AF XY: 0.000312 AC XY: 227 AN XY: 727244

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000536 AC: 14 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00329 AC: 284 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000396 AC: 44 AN: 1112008

Other (OTH) AF: 0.000199 AC: 12 AN: 60396

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74464

African (AFR) AF: 0.0000241 AC: 1 AN: 41554

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.000496 AC: 60

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CX3CR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Uncertain	0.42	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.069	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.0067	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.21
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.071
Sift	Benign	0.23	T
Sift4G	Benign	0.20	T
Polyphen		0.017	B
Vest4		0.096
MutPred		0.43		Gain of catalytic residue at V193 (P = 0.0615)
MVP		0.46
MPC		0.37
ClinPred		0.018	T
GERP RS		3.8
Varity_R		0.16
gMVP		0.51
Mutation Taster		=100/0	polymorphism

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: rs200607201; hg19: chr3-39307430; COSMIC: COSV100843243; COSMIC: COSV100843243;