9-127815124-T-C
Variant names:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001114753.3(ENG):c.*558A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000722 in 152,312 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ENG
NM_001114753.3 3_prime_UTR
NM_001114753.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0330
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 9-127815124-T-C is Benign according to our data. Variant chr9-127815124-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 914942.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.*558A>G | 3_prime_UTR_variant | Exon 15 of 15 | ENST00000373203.9 | NP_001108225.1 | ||
ENG | NM_000118.4 | c.*793A>G | 3_prime_UTR_variant | Exon 14 of 14 | NP_000109.1 | |||
ENG | NM_001278138.2 | c.*558A>G | 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.*558A>G | 3_prime_UTR_variant | Exon 15 of 15 | 1 | NM_001114753.3 | ENSP00000362299.4 | |||
ENG | ENST00000344849 | c.*793A>G | 3_prime_UTR_variant | Exon 14 of 14 | 1 | ENSP00000341917.3 | ||||
ENG | ENST00000480266 | c.*558A>G | 3_prime_UTR_variant | Exon 15 of 15 | 2 | ENSP00000479015.1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152194Hom.: 0 Cov.: 33
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1012Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 490
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GnomAD4 genome AF: 0.0000722 AC: 11AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74470
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Telangiectasia, hereditary hemorrhagic, type 1 Benign:1
Likely benign, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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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