rs41355248
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001114753.3(ENG):c.360+21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 1,613,686 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.017 ( 71 hom., cov: 31)
Exomes 𝑓: 0.0019 ( 73 hom. )
Consequence
ENG
NM_001114753.3 intron
NM_001114753.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.437
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 9-127829666-G-A is Benign according to our data. Variant chr9-127829666-G-A is described in ClinVar as [Benign]. Clinvar id is 255145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0571 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.360+21C>T | intron_variant | ENST00000373203.9 | |||
ENG | NM_000118.4 | c.360+21C>T | intron_variant | ||||
ENG | NM_001278138.2 | c.-187+21C>T | intron_variant | ||||
ENG | NM_001406715.1 | c.360+21C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.360+21C>T | intron_variant | 1 | NM_001114753.3 | P2 | |||
ENG | ENST00000344849.4 | c.360+21C>T | intron_variant | 1 | A2 | ||||
ENG | ENST00000480266.6 | c.-187+21C>T | intron_variant | 2 | |||||
ENG | ENST00000462196.1 | n.118+21C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0172 AC: 2620AN: 152138Hom.: 71 Cov.: 31
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GnomAD3 exomes AF: 0.00475 AC: 1188AN: 250204Hom.: 30 AF XY: 0.00353 AC XY: 478AN XY: 135314
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GnomAD4 exome AF: 0.00191 AC: 2792AN: 1461430Hom.: 73 Cov.: 31 AF XY: 0.00164 AC XY: 1195AN XY: 727008
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GnomAD4 genome ? AF: 0.0173 AC: 2630AN: 152256Hom.: 71 Cov.: 31 AF XY: 0.0170 AC XY: 1265AN XY: 74440
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 15, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 01, 2018 | - - |
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