3-39281174-A-G

Variant names:

• chr3-39281174-A-G
• rs938203
• NM_001171171.2:c.-141T>C

Variant summary

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

The NM_001171171.2(CX3CR1):​c.-141T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 1,016,012 control chromosomes in the GnomAD database, including 387,192 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.84 (54508 hom., cov: 31)
  • Exomes 𝑓: 0.88 (332684 hom.)
• Consequence: CX3CR1 NM_001171171.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532
• Publications: 9 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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CX3CR1	NM_001171171.2	c.-141T>C		5_prime_UTR_variant	Exon 1 of 2		NP_001164642.1
CX3CR1	NM_001171174.1	c.87+435T>C		intron_variant	Intron 1 of 1		NP_001164645.1
CX3CR1	XM_047447538.1	c.-10+11618T>C		intron_variant	Intron 1 of 1		XP_047303494.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CX3CR1	ENST00000541347.5	c.-141T>C		5_prime_UTR_variant	Exon 1 of 2	4		ENSP00000439140.1
CX3CR1	ENST00000412814.1	c.-141T>C		5_prime_UTR_variant	Exon 1 of 2	4		ENSP00000408835.1
CX3CR1	ENST00000358309.3	c.87+435T>C		intron_variant	Intron 1 of 1	2		ENSP00000351059.3

Frequencies

GnomAD3 genomes AF: 0.844 AC: 128372 AN: 152050 Hom.: 54481 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.838

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.851

GnomAD4 exome AF: 0.877 AC: 757777 AN: 863844 Hom.: 332684 Cov.: 32 AF XY: 0.877 AC XY: 351911 AN XY: 401158

African (AFR) AF: 0.739 AC: 11952 AN: 16180

American (AMR) AF: 0.880 AC: 2768 AN: 3144

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 4870 AN: 5684

East Asian (EAS) AF: 0.953 AC: 4073 AN: 4276

South Asian (SAS) AF: 0.861 AC: 18805 AN: 21848

European-Finnish (FIN) AF: 0.884 AC: 1354 AN: 1532

Middle Eastern (MID) AF: 0.855 AC: 1480 AN: 1730

European-Non Finnish (NFE) AF: 0.881 AC: 687296 AN: 780516

Other (OTH) AF: 0.870 AC: 25179 AN: 28934

GnomAD4 genome AF: 0.844 AC: 128452 AN: 152168 Hom.: 54508 Cov.: 31 AF XY: 0.844 AC XY: 62798 AN XY: 74374

African (AFR) AF: 0.746 AC: 30946 AN: 41496

American (AMR) AF: 0.865 AC: 13245 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2978 AN: 3470

East Asian (EAS) AF: 0.956 AC: 4928 AN: 5154

South Asian (SAS) AF: 0.865 AC: 4169 AN: 4820

European-Finnish (FIN) AF: 0.886 AC: 9397 AN: 10604

Middle Eastern (MID) AF: 0.846 AC: 247 AN: 292

European-Non Finnish (NFE) AF: 0.881 AC: 59882 AN: 68004

Other (OTH) AF: 0.848 AC: 1791 AN: 2112

Alfa AF: 0.858 Hom.: 7096

Bravo AF: 0.838

Asia WGS AF: 0.906 AC: 3150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.40
PhyloP100		-0.53
PromoterAI		-0.025	Neutral
Mutation Taster		=287/13	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs938203; hg19: chr3-39322665;