rs781068454
Positions:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_000071.3(CBS):c.737-9G>A variant causes a splice polypyrimidine tract, intron 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 0.00022 ( 0 hom., cov: 2)
Exomes 𝑓: 0.000037 ( 2 hom. )
Failed GnomAD Quality Control
Consequence
CBS
NM_000071.3 splice_polypyrimidine_tract, intron
NM_000071.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00007592
2
Clinical Significance
Conservation
PhyloP100: 0.0330
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 Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 21-43064000-C-T is Benign according to our data. Variant chr21-43064000-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 471367.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CBS | NM_000071.3 | c.737-9G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000398165.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CBS | ENST00000398165.8 | c.737-9G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000071.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 4538Hom.: 0 Cov.: 2 FAILED QC
GnomAD3 genomes
?
AF:
AC:
1
AN:
4538
Hom.:
Cov.:
2
FAILED QC
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000382 AC: 9AN: 235674Hom.: 0 AF XY: 0.0000392 AC XY: 5AN XY: 127474
GnomAD3 exomes
AF:
AC:
9
AN:
235674
Hom.:
AF XY:
AC XY:
5
AN XY:
127474
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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000371 AC: 6AN: 161840Hom.: 2 Cov.: 0 AF XY: 0.0000232 AC XY: 2AN XY: 86338
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
6
AN:
161840
Hom.:
Cov.:
0
AF XY:
AC XY:
2
AN XY:
86338
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.000220 AC: 1AN: 4538Hom.: 0 Cov.: 2 AF XY: 0.000482 AC XY: 1AN XY: 2076
GnomAD4 genome
?
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
4538
Hom.:
Cov.:
2
AF XY:
AC XY:
1
AN XY:
2076
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 11, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at