rs115450389
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_001114753.3(ENG):c.1452C>T(p.Ser484=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000899 in 1,613,796 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0029 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00069 ( 3 hom. )
Consequence
ENG
NM_001114753.3 synonymous
NM_001114753.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.29
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 -16 ACMG points.
BP6
?
Variant 9-127818354-G-A is Benign according to our data. Variant chr9-127818354-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-127818354-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00295 (449/152334) while in subpopulation AFR AF= 0.00873 (363/41562). AF 95% confidence interval is 0.00799. There are 3 homozygotes in gnomad4. There are 205 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 449 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.1452C>T | p.Ser484= | synonymous_variant | 12/15 | ENST00000373203.9 | |
LOC102723566 | NR_136302.1 | n.1421G>A | non_coding_transcript_exon_variant | 3/6 | |||
ENG | NM_000118.4 | c.1452C>T | p.Ser484= | synonymous_variant | 12/14 | ||
ENG | NM_001278138.2 | c.906C>T | p.Ser302= | synonymous_variant | 12/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.1452C>T | p.Ser484= | synonymous_variant | 12/15 | 1 | NM_001114753.3 | P2 | |
ENST00000439298.5 | n.1421G>A | non_coding_transcript_exon_variant | 3/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00293 AC: 446AN: 152216Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00112 AC: 279AN: 248912Hom.: 0 AF XY: 0.000890 AC XY: 120AN XY: 134806
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GnomAD4 exome AF: 0.000686 AC: 1002AN: 1461462Hom.: 3 Cov.: 31 AF XY: 0.000640 AC XY: 465AN XY: 727002
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GnomAD4 genome ? AF: 0.00295 AC: 449AN: 152334Hom.: 3 Cov.: 32 AF XY: 0.00275 AC XY: 205AN XY: 74490
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Telangiectasia, hereditary hemorrhagic, type 1 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 13, 2019 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 11, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | ENG: BS2 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Hereditary hemorrhagic telangiectasia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 16, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
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
DS_AG_spliceai
Position offset: -16
Find out detailed SpliceAI scores and Pangolin per-transcript scores at