rs2164611

Positions:

• chr6-80458392-C-T

Variant summary

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

The NM_001424037.1(BCKDHB):​c.1039-4480C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 152,176 control chromosomes in the GnomAD database, including 2,279 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 0.099 (2279 hom., cov: 32)
• Consequence: BCKDHB NM_001424037.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

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]

ENSG00000233967 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCKDHB	NM_001424037.1	c.1039-4480C>T		intron_variant			NP_001410966.1
BCKDHB	XR_001743546.3	n.1062-4480C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000233967	ENST00000427048.7	n.2467+4165C>T		intron_variant		3
ENSG00000233967	ENST00000443221.2	n.181+4165C>T		intron_variant		3
ENSG00000233967	ENST00000452402.6	n.301-4480C>T		intron_variant		2
ENSG00000233967	ENST00000656173.1	n.996-4480C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 15066 AN: 152058 Hom.: 2271 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.00587

Gnomad OTH AF: 0.0712

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

GnomAD4 genome AF: 0.0992 AC: 15098 AN: 152176 Hom.: 2279 Cov.: 32 AF XY: 0.0970 AC XY: 7220 AN XY: 74408

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.0509

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0107

Gnomad4 NFE AF: 0.00587

Gnomad4 OTH AF: 0.0699

Alfa AF: 0.0741 Hom.: 254

Bravo AF: 0.112

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.9
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2164611; hg19: chr6-81168109;