rs373962057
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_000071.3(CBS):c.1338G>A(p.Ala446=) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A446A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 0)
Consequence
CBS
NM_000071.3 synonymous
NM_000071.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.08
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
Variant 21-43058854-C-T is Benign according to our data. Variant chr21-43058854-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 413350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43058854-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2.08 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CBS | NM_000071.3 | c.1338G>A | p.Ala446= | synonymous_variant | 14/17 | ENST00000398165.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CBS | ENST00000398165.8 | c.1338G>A | p.Ala446= | synonymous_variant | 14/17 | 1 | NM_000071.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 0
GnomAD3 genomes
?
Cov.:
0
GnomAD3 exomes AF: 0.0000660 AC: 11AN: 166728Hom.: 0 AF XY: 0.0000678 AC XY: 6AN XY: 88486
GnomAD3 exomes
AF:
AC:
11
AN:
166728
Hom.:
AF XY:
AC XY:
6
AN XY:
88486
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
GnomAD4 genome ? Cov.: 0
GnomAD4 genome
?
Cov.:
0
Asia WGS
AF:
AC:
36
AN:
3478
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 | Apr 03, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 27, 2019 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2016 | 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 | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at