rs754246295

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

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.161
Variant links:
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=-0.38).
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
CBSNM_000071.3 linkuse as main transcriptc.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
CBSENST00000398165.8 linkuse as main transcriptc.501C>T p.Ile167= synonymous_variant 6/171 NM_000071.3 ENSP00000381231 P1P35520-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
1282
Hom.:
0
Cov.:
0
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000375
AC:
7
AN:
186604
Hom.:
0
AF XY:
0.0000200
AC XY:
2
AN XY:
100032
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000141
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000401
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000256
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000302
AC:
9
AN:
298174
Hom.:
3
Cov.:
0
AF XY:
0.0000127
AC XY:
2
AN XY:
157150
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000344
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000494
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000122
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1282
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
640
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

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 submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesOct 26, 2023- -
Likely benign, criteria provided, single submitterclinical testingGeneDxNov 20, 2019- -
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJun 02, 2017This 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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 18, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
CADD
Benign
11
DANN
Benign
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs754246295; hg19: chr21-44485756; API