rs370167302

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000071.3(CBS):c.429C>T(p.Ile143Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000344 in 1,190,562 control chromosomes in the GnomAD database, including 10 homozygotes. 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: 15)

Exomes 𝑓: 0.000034 ( 10 hom. )

Failed GnomAD Quality Control

Consequence

CBS
NM_000071.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.47

Publications

2 publications found

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]

CBS Gene-Disease associations (from GenCC):

classic homocystinuria
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, PanelApp Australia, ClinGen, Genomics England PanelApp

CBS links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 21-43066265-G-A is Benign according to our data. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-43066265-G-A is described in CliVar as Likely_benign. Clinvar id is 538703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.47 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBS	NM_000071.3 link	c.429C>T	p.Ile143Ile	synonymous_variant	Exon 5 of 17	ENST00000398165.8	NP_000062.1	P35520-1Q9NTF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBS	ENST00000398165.8 link	c.429C>T	p.Ile143Ile	synonymous_variant	Exon 5 of 17	1	NM_000071.3	ENSP00000381231.4		P35520-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

110952

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

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

GnomAD2 exomes

AF:

0.0000320

AC:

AN:

250052

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000344

AC:

AN:

1190562

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

597544

show subpopulations

African (AFR)

AF:

0.0000536

AC:

AN:

18658

American (AMR)

AF:

0.0000236

AC:

AN:

42434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21842

East Asian (EAS)

AF:

0.000129

AC:

AN:

38794

South Asian (SAS)

AF:

0.00

AC:

AN:

76082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4310

European-Non Finnish (NFE)

AF:

0.0000145

AC:

AN:

898536

Other (OTH)

AF:

0.000418

AC:

AN:

50288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

110952

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

53950

African (AFR)

AF:

0.00

AC:

AN:

20372

American (AMR)

AF:

0.00

AC:

AN:

12632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2810

East Asian (EAS)

AF:

0.00

AC:

AN:

4766

South Asian (SAS)

AF:

0.00

AC:

AN:

3644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8722

Middle Eastern (MID)

AF:

0.00

AC:

AN:

220

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

55452

Other (OTH)

AF:

0.00

AC:

AN:

1562

Alfa

AF:

0.0000959

Hom.:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Jan 10, 2020

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

May 26, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.1

(source)

DANN

Benign

0.80

PhyloP100

-1.5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over