rs8132811

chr21-43055767-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_000071.3(CBS):c.1552+1036G>A 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: 17)
• Consequence: CBS NM_000071.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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 Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 21-43055767-C-T is Benign according to our data. Variant chr21-43055767-C-T is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAdExome at 2039 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBS	NM_000071.3	c.1552+1036G>A		intron_variant		ENST00000398165.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBS	ENST00000398165.8	c.1552+1036G>A		intron_variant		1	NM_000071.3	P1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD3 exomes AF: 0.188 AC: 18632 AN: 99246 Hom.: 2039 AF XY: 0.187 AC XY: 10045 AN XY: 53762

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.0952

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.0797

Gnomad SAS exome AF: 0.159

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.178

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 17

Alfa AF: 0.224 Hom.: 959

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.5
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs8132811; hg19: chr21-44475877; COSMIC: COSV61446579; COSMIC: COSV61446579;