3-39281174-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001171171.2(CX3CR1):​c.-141T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000116 in 863,992 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: CX3CR1 NM_001171171.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.532
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CX3CR1	NM_001171171.2	c.-141T>A		5_prime_UTR_variant	Exon 1 of 2		NP_001164642.1
CX3CR1	NM_001171174.1	c.87+435T>A		intron_variant	Intron 1 of 1		NP_001164645.1
CX3CR1	XM_047447538.1	c.-10+11618T>A		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>A		5_prime_UTR_variant	Exon 1 of 2	4		ENSP00000439140.1
CX3CR1	ENST00000412814.1	c.-141T>A		5_prime_UTR_variant	Exon 1 of 2	4		ENSP00000408835.1
CX3CR1	ENST00000358309.3	c.87+435T>A		intron_variant	Intron 1 of 1	2		ENSP00000351059.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000116 AC: 1 AN: 863992 Hom.: 0 Cov.: 32 AF XY: 0.00000249 AC XY: 1 AN XY: 401226

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 16186

American (AMR) AF: 0.00 AC: 0 AN: 3156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5684

East Asian (EAS) AF: 0.00 AC: 0 AN: 4278

South Asian (SAS) AF: 0.00 AC: 0 AN: 21862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1730

European-Non Finnish (NFE) AF: 0.00000128 AC: 1 AN: 780622

Other (OTH) AF: 0.00 AC: 0 AN: 28938

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.43
PhyloP100		-0.53
PromoterAI		-0.012	Neutral

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;