rs688867

Positions:

• chr6-80229511-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183050.4(BCKDHB):​c.951+26299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,018 control chromosomes in the GnomAD database, including 7,934 homozygotes. 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: 𝑓 0.31 (7934 hom., cov: 32)
• Consequence: BCKDHB NM_183050.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCKDHB	NM_183050.4	c.951+26299G>A		intron_variant		ENST00000320393.9	NP_898871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCKDHB	ENST00000320393.9	c.951+26299G>A		intron_variant		1	NM_183050.4	ENSP00000318351	P1
BCKDHB	ENST00000356489.9	c.951+26299G>A		intron_variant		1		ENSP00000348880	P1
BCKDHB	ENST00000468520.1	n.112-22201G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47510 AN: 151900 Hom.: 7937 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.313 AC: 47508 AN: 152018 Hom.: 7934 Cov.: 32 AF XY: 0.310 AC XY: 23067 AN XY: 74292

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.312

Alfa AF: 0.363 Hom.: 10293

Bravo AF: 0.306

Asia WGS AF: 0.238 AC: 825 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	4.1
DANN	Benign	0.52

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: rs688867; hg19: chr6-80939228; COSMIC: COSV57517835;