rs779103881
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_001114753.3(ENG):c.1273-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000933 in 1,608,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001114753.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.1273-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000373203.9 | |||
LOC102723566 | NR_136302.1 | n.1568+954G>A | intron_variant, non_coding_transcript_variant | ||||
ENG | NM_000118.4 | c.1273-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
ENG | NM_001278138.2 | c.727-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.1273-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001114753.3 | P2 | |||
ENST00000439298.5 | n.1568+954G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000423 AC: 1AN: 236366Hom.: 0 AF XY: 0.00000782 AC XY: 1AN XY: 127818
GnomAD4 exome AF: 0.00000893 AC: 13AN: 1455894Hom.: 0 Cov.: 32 AF XY: 0.00000829 AC XY: 6AN XY: 723672
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 22, 2021 | DNA sequence analysis of the ENG gene demonstrated a sequence change in intron 9, c.1273-5C>T. This sequence change has been described in the gnomAD database in one individual which corresponds to a population frequency of 0.00042% (dbSNP rs779103881). This sequence change is not predicted to have a deleterious effect on splicing based on in-silico splice prediction programs. This change does not appear to have been previously described in individuals with ENG-related disorders. It is possible that this sequence change represents a benign sequence change in the ENG gene that has not been identified to date. The functional significance of this sequence change is not known at present and its contribution to this individual's disease phenotype cannot definitively be determined. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 19, 2016 | - - |
Telangiectasia, hereditary hemorrhagic, type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 30, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Hereditary hemorrhagic telangiectasia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 29, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at