rs754246295
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_000071.3(CBS):c.501C>T(p.Ile167=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000030 ( 3 hom. )
Failed GnomAD Quality Control
Consequence
CBS
NM_000071.3 synonymous
NM_000071.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.161
Genes affected
CBS (HGNC:1550): (cystathionine beta-synthase) The protein encoded by this gene acts as a homotetramer to catalyze the conversion of homocysteine to cystathionine, the first step in the transsulfuration pathway. The encoded protein is allosterically activated by adenosyl-methionine and uses pyridoxal phosphate as a cofactor. Defects in this gene can cause cystathionine beta-synthase deficiency (CBSD), which can lead to homocystinuria. This gene is a major contributor to cellular hydrogen sulfide production. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
Variant 21-43065646-G-A is Benign according to our data. Variant chr21-43065646-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 381476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43065646-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.161 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CBS | NM_000071.3 | c.501C>T | p.Ile167= | synonymous_variant | 6/17 | ENST00000398165.8 | NP_000062.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CBS | ENST00000398165.8 | c.501C>T | p.Ile167= | synonymous_variant | 6/17 | 1 | NM_000071.3 | ENSP00000381231 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 1282Hom.: 0 Cov.: 0 FAILED QC
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GnomAD3 exomes AF: 0.0000375 AC: 7AN: 186604Hom.: 0 AF XY: 0.0000200 AC XY: 2AN XY: 100032
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000302 AC: 9AN: 298174Hom.: 3 Cov.: 0 AF XY: 0.0000127 AC XY: 2AN XY: 157150
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GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1282Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 640
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 26, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 20, 2019 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 02, 2017 | This alteration is classified as likely 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. - |
HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 18, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at