NM_001337.4:c.839C>T

Variant names:

• chr3-39265671-G-A
• rs3732378
• NM_001337.4:c.839C>T

Variant summary

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

The NM_001337.4(CX3CR1):​c.839C>T​(p.Thr280Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,613,948 control chromosomes in the GnomAD database, including 21,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.12 (1435 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19635 hom.)
• Consequence: CX3CR1 NM_001337.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 269 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=0.0025131404).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

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.839C>T	p.Thr280Met	missense	Exon 2 of 2	NP_001328.1	P49238-1
	CX3CR1	NM_001171174.1		c.935C>T	p.Thr312Met	missense	Exon 2 of 2	NP_001164645.1	P49238-4
	CX3CR1	NM_001171171.2		c.839C>T	p.Thr280Met	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.839C>T	p.Thr280Met	missense	Exon 2 of 2	ENSP00000382166.3	P49238-1
	CX3CR1	ENST00000358309.3	TSL:2	c.935C>T	p.Thr312Met	missense	Exon 2 of 2	ENSP00000351059.3	P49238-4
	CX3CR1	ENST00000541347.5	TSL:4	c.839C>T	p.Thr280Met	missense	Exon 2 of 2	ENSP00000439140.1	P49238-1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18378 AN: 152028 Hom.: 1431 Cov.: 32

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.140 AC: 34826 AN: 249502 AF XY: 0.139

Gnomad AFR exome AF: 0.0303

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.0217

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.139

GnomAD4 exome AF: 0.159 AC: 232796 AN: 1461802 Hom.: 19635 Cov.: 33 AF XY: 0.158 AC XY: 114842 AN XY: 727212

African (AFR) AF: 0.0265 AC: 888 AN: 33480

American (AMR) AF: 0.158 AC: 7060 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4831 AN: 26136

East Asian (EAS) AF: 0.0335 AC: 1331 AN: 39698

South Asian (SAS) AF: 0.102 AC: 8783 AN: 86258

European-Finnish (FIN) AF: 0.159 AC: 8505 AN: 53420

Middle Eastern (MID) AF: 0.0910 AC: 525 AN: 5768

European-Non Finnish (NFE) AF: 0.173 AC: 192049 AN: 1111926

Other (OTH) AF: 0.146 AC: 8824 AN: 60394

GnomAD4 genome AF: 0.121 AC: 18394 AN: 152146 Hom.: 1435 Cov.: 32 AF XY: 0.120 AC XY: 8947 AN XY: 74372

African (AFR) AF: 0.0329 AC: 1365 AN: 41518

American (AMR) AF: 0.133 AC: 2029 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3470

East Asian (EAS) AF: 0.0253 AC: 131 AN: 5178

South Asian (SAS) AF: 0.104 AC: 504 AN: 4826

European-Finnish (FIN) AF: 0.167 AC: 1759 AN: 10556

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.171 AC: 11655 AN: 67996

Other (OTH) AF: 0.117 AC: 248 AN: 2114

Alfa AF: 0.153 Hom.: 9539

Bravo AF: 0.114

TwinsUK AF: 0.178 AC: 661

ALSPAC AF: 0.178 AC: 685

ESP6500AA AF: 0.0322 AC: 126

ESP6500EA AF: 0.172 AC: 1432

ExAC AF: 0.136 AC: 16453

Asia WGS AF: 0.0810 AC: 279 AN: 3478

EpiCase AF: 0.162

EpiControl AF: 0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.026
Eigen_PC	Benign	0.0021
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.9
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.77	P
Vest4		0.27
MPC		0.46
ClinPred		0.028	T
GERP RS		4.0
Varity_R		0.092
gMVP		0.30
Mutation Taster		=97/3	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: rs3732378; hg19: chr3-39307162; COSMIC: COSV64193810; COSMIC: COSV64193810;