9-127815416-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001114753.3(ENG):c.*266G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 547,094 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00026 ( 1 hom. )
Consequence
ENG
NM_001114753.3 3_prime_UTR
NM_001114753.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.415
Genes affected
ENG (HGNC:3349): (endoglin) This gene encodes a homodimeric transmembrane protein which is a major glycoprotein of the vascular endothelium. This protein is a component of the transforming growth factor beta receptor complex and it binds to the beta1 and beta3 peptides with high affinity. Mutations in this gene cause hereditary hemorrhagic telangiectasia, also known as Osler-Rendu-Weber syndrome 1, an autosomal dominant multisystemic vascular dysplasia. This gene may also be involved in preeclampsia and several types of cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BS2
High AC in GnomAd4 at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.*266G>A | 3_prime_UTR_variant | Exon 15 of 15 | ENST00000373203.9 | NP_001108225.1 | ||
ENG | NM_000118.4 | c.*501G>A | 3_prime_UTR_variant | Exon 14 of 14 | NP_000109.1 | |||
ENG | NM_001278138.2 | c.*266G>A | 3_prime_UTR_variant | Exon 15 of 15 | NP_001265067.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203 | c.*266G>A | 3_prime_UTR_variant | Exon 15 of 15 | 1 | NM_001114753.3 | ENSP00000362299.4 | |||
ENG | ENST00000344849 | c.*501G>A | 3_prime_UTR_variant | Exon 14 of 14 | 1 | ENSP00000341917.3 | ||||
ENG | ENST00000480266 | c.*266G>A | 3_prime_UTR_variant | Exon 15 of 15 | 2 | ENSP00000479015.1 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152232Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.000261 AC: 103AN: 394862Hom.: 1 Cov.: 5 AF XY: 0.000217 AC XY: 44AN XY: 202756
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74362
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Telangiectasia, hereditary hemorrhagic, type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at