NM_001337.4:c.765G>A

Variant names:

• chr3-39265745-C-T
• rs55975803
• NM_001337.4:c.765G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001337.4(CX3CR1):​c.765G>A​(p.Thr255Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,614,186 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (12 hom.)
• Consequence: CX3CR1 NM_001337.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -9.13
• Publications: 1 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-39265745-C-T is Benign according to our data. Variant chr3-39265745-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 788850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-9.13 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 12 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.765G>A	p.Thr255Thr	synonymous	Exon 2 of 2	NP_001328.1	P49238-1
	CX3CR1	NM_001171174.1		c.861G>A	p.Thr287Thr	synonymous	Exon 2 of 2	NP_001164645.1	P49238-4
	CX3CR1	NM_001171171.2		c.765G>A	p.Thr255Thr	synonymous	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.765G>A	p.Thr255Thr	synonymous	Exon 2 of 2	ENSP00000382166.3	P49238-1
	CX3CR1	ENST00000358309.3	TSL:2	c.861G>A	p.Thr287Thr	synonymous	Exon 2 of 2	ENSP00000351059.3	P49238-4
	CX3CR1	ENST00000541347.5	TSL:4	c.765G>A	p.Thr255Thr	synonymous	Exon 2 of 2	ENSP00000439140.1	P49238-1

Frequencies

GnomAD3 genomes AF: 0.00317 AC: 482 AN: 152194 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00707

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00517

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00368 AC: 917 AN: 249482 AF XY: 0.00335

Gnomad AFR exome AF: 0.000904

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.000993

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00580

Gnomad NFE exome AF: 0.00619

Gnomad OTH exome AF: 0.00314

GnomAD4 exome AF: 0.00425 AC: 6217 AN: 1461874 Hom.: 12 Cov.: 33 AF XY: 0.00401 AC XY: 2916 AN XY: 727238

African (AFR) AF: 0.000597 AC: 20 AN: 33480

American (AMR) AF: 0.00145 AC: 65 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000650 AC: 17 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00635 AC: 339 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00503 AC: 5595 AN: 1111994

Other (OTH) AF: 0.00291 AC: 176 AN: 60394

GnomAD4 genome AF: 0.00316 AC: 482 AN: 152312 Hom.: 1 Cov.: 32 AF XY: 0.00318 AC XY: 237 AN XY: 74474

African (AFR) AF: 0.000674 AC: 28 AN: 41566

American (AMR) AF: 0.00111 AC: 17 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00707 AC: 75 AN: 10610

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

European-Non Finnish (NFE) AF: 0.00517 AC: 352 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00466 Hom.: 2

Bravo AF: 0.00280

EpiCase AF: 0.00376

EpiControl AF: 0.00439

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.14
DANN	Benign	0.66
PhyloP100		-9.1
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: rs55975803; hg19: chr3-39307236;