ENST00000461686.5:n.2070_2074delCTGGC

Variant names:

• chr21-43053772-TGCCAG-T
• rs71872941
• ENST00000461686.5:n.2070_2074delCTGGC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000461686.5(CBS):​n.2070_2074delCTGGC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: CBS ENST00000461686.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.283
• Publications: 3 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 21-43053772-TGCCAG-T is Benign according to our data. Variant chr21-43053772-TGCCAG-T is described in ClinVar as Benign. ClinVar VariationId is 340077.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000461686.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBS	NM_000071.3	MANE Select	c.*103_*107delCTGGC		3_prime_UTR	Exon 17 of 17	NP_000062.1
	CBS	NM_001178008.3		c.*103_*107delCTGGC		3_prime_UTR	Exon 17 of 17	NP_001171479.1
	CBS	NM_001320298.2		c.*103_*107delCTGGC		3_prime_UTR	Exon 18 of 18	NP_001307227.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBS	ENST00000461686.5	TSL:1	n.2070_2074delCTGGC		non_coding_transcript_exon	Exon 14 of 14
	CBS	ENST00000398165.8	TSL:1 MANE Select	c.*103_*107delCTGGC		3_prime_UTR	Exon 17 of 17	ENSP00000381231.4
	CBS	ENST00000352178.9	TSL:1	c.*103_*107delCTGGC		3_prime_UTR	Exon 17 of 17	ENSP00000344460.5

Frequencies

GnomAD3 genomes Cov.: 0

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 0

Alfa AF: 0.0472 Hom.: 4

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Homocystinuria Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs71872941; hg19: chr21-44473882; COSMIC: COSV61442018; COSMIC: COSV61442018;