9-127819616-T-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001114753.3(ENG):c.1311+6A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001114753.3 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.1311+6A>G | splice_region_variant, intron_variant | Intron 10 of 14 | ENST00000373203.9 | NP_001108225.1 | ||
ENG | NM_000118.4 | c.1311+6A>G | splice_region_variant, intron_variant | Intron 10 of 13 | NP_000109.1 | |||
ENG | NM_001278138.2 | c.765+6A>G | splice_region_variant, intron_variant | Intron 10 of 14 | NP_001265067.1 | |||
LOC102723566 | NR_136302.1 | n.1568+905T>C | intron_variant | Intron 4 of 5 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000805 AC: 2AN: 248538Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134650
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460894Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726712
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74354
ClinVar
Submissions by phenotype
Hereditary hemorrhagic telangiectasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 27, 2016 | This sequence change falls in intron 10 of the ENG gene. It does not directly change the encoded amino acid sequence of the ENG protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ENG-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a novel intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at