rs234713

Positions:

• chr21-43067781-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_000071.3(CBS):​c.316+728C>T variant causes a 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 Lovd as Benign (no stars).

• Frequency: Genomes: not found (cov: 14)
• Consequence: CBS NM_000071.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 21-43067781-G-A is Benign according to our data. Variant chr21-43067781-G-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBS	NM_000071.3	c.316+728C>T		intron_variant		ENST00000398165.8	NP_000062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBS	ENST00000398165.8	c.316+728C>T		intron_variant		1	NM_000071.3	ENSP00000381231	P1

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD3 exomes AF: 0.253 AC: 33925 AN: 134230 Hom.: 4956 AF XY: 0.259 AC XY: 18948 AN XY: 73104

Gnomad AFR exome AF: 0.348

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.0272

Gnomad SAS exome AF: 0.251

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.328

Gnomad OTH exome AF: 0.265

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 14

Alfa AF: 0.292 Hom.: 610

Asia WGS AF: 0.137 AC: 478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	12
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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

Other links and lift over

dbSNP: rs234713; hg19: chr21-44487891;