rs1554180622

Variant names:

• chr6-80106626-CGGGTGCTCCGCCCTCCCCGCAGGCGGCGTGCGGCTGCATAGCCTGAGAATCCCGGTGGTGAGCGGGGATGGCGGTTGTAGCGGCGGCTGCCGGCTGGCTACTCAGGCTCAGGGCGGCAGGGGCTGAGGGGCACTGGCGTCGGCTTCCTGGCGCGGGGCTGGCGCGGGGCTTTTTGCACCCCGCCGCGACTGTCGAGGATGCGGCCCAGAGGCGGCAGGTGGCTCATTTTACTTTCCAGCCAGATCCGGAGCCCCGGGAGTACG-C
• rs1554180622
• ENST00000320393:c.-67_185+11del

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_183050.4(BCKDHB):​c.-66_196+1del variant causes a exon loss, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCKDHB NM_183050.4 exon_loss, splice_region
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.810

Genes affected

BCKDHB (HGNC:987): (branched chain keto acid dehydrogenase E1 subunit beta) This gene encodes the E1 beta subunit of branched-chain keto acid dehydrogenase, which is a multienzyme complex associated with the inner membrane of mitochondria. This enzyme complex functions in the catabolism of branched-chain amino acids. Mutations in this gene have been associated with maple syrup urine disease (MSUD), type 1B, a disease characterized by a maple syrup odor to the urine in addition to mental and physical retardation and feeding problems. Alternative splicing at this locus results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-80106626-CGGGTGCTCCGCCCTCCCCGCAGGCGGCGTGCGGCTGCATAGCCTGAGAATCCCGGTGGTGAGCGGGGATGGCGGTTGTAGCGGCGGCTGCCGGCTGGCTACTCAGGCTCAGGGCGGCAGGGGCTGAGGGGCACTGGCGTCGGCTTCCTGGCGCGGGGCTGGCGCGGGGCTTTTTGCACCCCGCCGCGACTGTCGAGGATGCGGCCCAGAGGCGGCAGGTGGCTCATTTTACTTTCCAGCCAGATCCGGAGCCCCGGGAGTACG-C is Pathogenic according to our data. Variant chr6-80106626-CGGGTGCTCCGCCCTCCCCGCAGGCGGCGTGCGGCTGCATAGCCTGAGAATCCCGGTGGTGAGCGGGGATGGCGGTTGTAGCGGCGGCTGCCGGCTGGCTACTCAGGCTCAGGGCGGCAGGGGCTGAGGGGCACTGGCGTCGGCTTCCTGGCGCGGGGCTGGCGCGGGGCTTTTTGCACCCCGCCGCGACTGTCGAGGATGCGGCCCAGAGGCGGCAGGTGGCTCATTTTACTTTCCAGCCAGATCCGGAGCCCCGGGAGTACG-C is described in ClinVar as [Pathogenic]. Clinvar id is 224058.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCKDHB	NM_183050.4	c.-66_196+1del		exon_loss_variant, splice_region_variant	Exon 1 of 10	ENST00000320393.9	NP_898871.1
BCKDHB	NM_183050.4	c.-66_185+12del		splice_donor_variant, 5_prime_UTR_truncation, exon_loss_variant, intron_variant	Exon 1 of 10	ENST00000320393.9	NP_898871.1
BCKDHB	NM_183050.4	c.-67_196del		upstream_gene_variant		ENST00000320393.9	NP_898871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCKDHB	ENST00000320393	c.-67_185+11del		5_prime_UTR_truncation, exon_loss_variant	Exon 1 of 10	1	NM_183050.4	ENSP00000318351.5
BCKDHB	ENST00000320393.9	c.-67_196del		exon_loss_variant, splice_region_variant	Exon 1 of 10	1	NM_183050.4	ENSP00000318351.5
BCKDHB	ENST00000320393.9	c.-67_196del		upstream_gene_variant		1	NM_183050.4	ENSP00000318351.5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Maple syrup urine disease Pathogenic:1

Jan 01, 2014

Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554180622; hg19: chr6-80816343;