rs185343653
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000020.3(ACVRL1):c.1246+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,612,110 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0089 ( 21 hom., cov: 33)
Exomes 𝑓: 0.00090 ( 20 hom. )
Consequence
ACVRL1
NM_000020.3 intron
NM_000020.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.479
Genes affected
ACVRL1 (HGNC:175): (activin A receptor like type 1) This gene encodes a type I cell-surface receptor for the TGF-beta superfamily of ligands. It shares with other type I receptors a high degree of similarity in serine-threonine kinase subdomains, a glycine- and serine-rich region (called the GS domain) preceding the kinase domain, and a short C-terminal tail. The encoded protein, sometimes termed ALK1, shares similar domain structures with other closely related ALK or activin receptor-like kinase proteins that form a subfamily of receptor serine/threonine kinases. Mutations in this gene are associated with hemorrhagic telangiectasia type 2, also known as Rendu-Osler-Weber syndrome 2. [provided by RefSeq, Jul 2008]
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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=-0.81).
BP6
Variant 12-51916252-C-T is Benign according to our data. Variant chr12-51916252-C-T is described in ClinVar as [Benign]. Clinvar id is 254707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-51916252-C-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00893 (1360/152272) while in subpopulation AFR AF= 0.0312 (1298/41568). AF 95% confidence interval is 0.0298. There are 21 homozygotes in gnomad4. There are 640 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1360 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACVRL1 | NM_000020.3 | c.1246+19C>T | intron_variant | ENST00000388922.9 | NP_000011.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00891 AC: 1355AN: 152154Hom.: 21 Cov.: 33
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GnomAD3 exomes AF: 0.00225 AC: 552AN: 245358Hom.: 13 AF XY: 0.00160 AC XY: 213AN XY: 132942
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GnomAD4 exome AF: 0.000903 AC: 1318AN: 1459838Hom.: 20 Cov.: 31 AF XY: 0.000778 AC XY: 565AN XY: 726136
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GnomAD4 genome AF: 0.00893 AC: 1360AN: 152272Hom.: 21 Cov.: 33 AF XY: 0.00860 AC XY: 640AN XY: 74448
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 08, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Telangiectasia, hereditary hemorrhagic, type 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2025 | - - |
Computational scores
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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