chr17-31095308-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001042492.3(NF1):c.-2A>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.000000722 in 1,385,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001042492.3 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.-2A>T | 5_prime_UTR_variant | Exon 1 of 58 | ENST00000358273.9 | NP_001035957.1 | ||
NF1 | NM_000267.3 | c.-2A>T | 5_prime_UTR_variant | Exon 1 of 57 | NP_000258.1 | |||
NF1 | NM_001128147.3 | c.-2A>T | 5_prime_UTR_variant | Exon 1 of 15 | NP_001121619.1 | |||
MIR4733HG | NR_186435.1 | n.183T>A | non_coding_transcript_exon_variant | Exon 1 of 4 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 30
GnomAD4 exome AF: 7.22e-7 AC: 1AN: 1385174Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 683388
GnomAD4 genome Cov.: 30
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Uncertain:1
The c.-2A>T variant is located in the 5' untranslated region (5’ UTR) of the NF1 gene. This variant results from an A to T substitution 2 bases upstream from the first translated codon. This nucleotide position is highly conserved in available vertebrate species. Based on the available evidence, the clinical significance of this alteration remains unclear. -
Hereditary cancer-predisposing syndrome Uncertain:1
The c.-2A>T variant is located in the 5' untranslated region (5’ UTR) of the NF1 gene. This variant results from an A to T substitution 2 bases upstream from the first translated codon. Although this alteration is near the initiation codon, it does not disrupt the key nucleotides of theKozak motif known to modulate translation initiation (KozakM, Cell 1986 Jan; 44(2):283-92). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 5109 samples (10218 alleles) with coverage at this position.To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 55000 alleles tested) in our clinical cohort.<span style="font-family:arial,sans-serif">Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at