rs757428597
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1
The NM_000071.3(CBS):c.737-1G>T variant causes a splice acceptor, intron change. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as (no stars).
Frequency
Genomes: not found (cov: 2)
Consequence
CBS
NM_000071.3 splice_acceptor, intron
NM_000071.3 splice_acceptor, intron
Scores
4
2
Splicing: ADA: 0.9999
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.85
Publications
0 publications found
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]
CBS Gene-Disease associations (from GenCC):
- classic homocystinuriaInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Myriad Women’s Health, Genomics England PanelApp
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 3.4, offset of 5, new splice context is: ttatccgtccaccatggaAGctg. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000071.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CBS | TSL:1 MANE Select | c.737-1G>T | splice_acceptor intron | N/A | ENSP00000381231.4 | P35520-1 | |||
| CBS | TSL:1 | c.737-1G>T | splice_acceptor intron | N/A | ENSP00000344460.5 | P35520-1 | |||
| CBS | TSL:1 | c.737-1G>T | splice_acceptor intron | N/A | ENSP00000352643.3 | P35520-1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
2
GnomAD2 exomes AF: 0.00 AC: 0AN: 241320 AF XY: 0.00
GnomAD2 exomes
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241320
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GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
GnomAD4 genome
GnomAD4 genome
Cov.:
2
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
PhyloP100
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 31
DS_AL_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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