rs2223876

Positions:

• chr6-80334322-G-A
• chr6-80334322-G-T

Variant summary

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

The NM_183050.4(BCKDHB):​c.1039-9342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 151,978 control chromosomes in the GnomAD database, including 46,135 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 0.78 (46135 hom., cov: 32)
• Consequence: BCKDHB NM_183050.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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]

BCKDHB (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCKDHB	NM_183050.4	c.1039-9342G>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.1039-9342G>A		intron_variant		1	NM_183050.4	ENSP00000318351.5
BCKDHB	ENST00000356489.9	c.1039-9342G>A		intron_variant		1		ENSP00000348880.5

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117866 AN: 151860 Hom.: 46108 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.776 AC: 117950 AN: 151978 Hom.: 46135 Cov.: 32 AF XY: 0.774 AC XY: 57509 AN XY: 74296

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.850

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.824

Gnomad4 OTH AF: 0.795

Alfa AF: 0.793 Hom.: 5982

Bravo AF: 0.778

Asia WGS AF: 0.670 AC: 2319 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.51

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: rs2223876; hg19: chr6-81044039;