Variant rs6586281 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_000071.3(CBS):c.1359-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.031 ( 0 hom. )

Consequence

CBS
NM_000071.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.471

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0313 (20/640) while in subpopulation NFE AF= 0.0565 (7/124). AF 95% confidence interval is 0.0265. There are 0 homozygotes in gnomad4_exome. There are 12 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBS	NM_000071.3 link	c.1359-30C>T		intron_variant		ENST00000398165.8	NP_000062.1	P35520-1Q9NTF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBS	ENST00000398165.8 link	c.1359-30C>T		intron_variant		1	NM_000071.3	ENSP00000381231.4		P35520-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.143

AC:

35430

AN:

248274

Hom.:

2851

AF XY:

0.142

AC XY:

19076

AN XY:

134492

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.00442

Gnomad SAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.0777

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.0313

AC:

AN:

640

Hom.:

Cov.:

AF XY:

0.0366

AC XY:

AN XY:

328

show subpopulations

Gnomad4 AMR exome

AF:

0.0283

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0172

Gnomad4 NFE exome

AF:

0.0565

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.151

Hom.:

161

Asia WGS

AF:

0.0700

AC:

244

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.19

DANN

Benign

0.63

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over