Variant rs200609312 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP6_Very_StrongBS1

The NM_183050.4(BCKDHB):c.197-11delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00753 in 1,395,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 0 hom. )

Consequence

BCKDHB
NM_183050.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.218

Variant links:

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 links:

BCKDHB (HGNC:):

BCKDHB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 6-80127535-TG-T is Benign according to our data. Variant chr6-80127535-TG-T is described in ClinVar as [Benign]. Clinvar id is 263076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-80127535-TG-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00844 (10498/1244034) while in subpopulation EAS AF= 0.0219 (611/27920). AF 95% confidence interval is 0.0204. There are 0 homozygotes in gnomad4_exome. There are 5147 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCKDHB	NM_183050.4 linkuse as main transcript	c.197-11delG		intron_variant		ENST00000320393.9	NP_898871.1	P21953-1A0A140VKB3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
BCKDHB	ENST00000320393.9 linkuse as main transcript	c.197-11delG	intron_variant	1	NM_183050.4	ENSP00000318351.5	P21953-1
BCKDHB	ENST00000356489.9 linkuse as main transcript	c.197-11delG	intron_variant	1		ENSP00000348880.5	P21953-1
BCKDHB	ENST00000369760.8 linkuse as main transcript	c.197-11delG	intron_variant	3		ENSP00000358775.4	P21953-2
BCKDHB	ENST00000486968.1 linkuse as main transcript	n.111-11delG	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151572

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000191

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000590

Gnomad OTH

AF:

0.000480

GnomAD4 exome

AF:

0.00844

AC:

10498

AN:

1244034

Hom.:

Cov.:

AF XY:

0.00836

AC XY:

5147

AN XY:

615650

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.0111

Gnomad4 ASJ exome

AF:

0.00661

Gnomad4 EAS exome

AF:

0.0219

Gnomad4 SAS exome

AF:

0.0142

Gnomad4 FIN exome

AF:

0.00699

Gnomad4 NFE exome

AF:

0.00786

Gnomad4 OTH exome

AF:

0.00943

GnomAD4 genome

AF:

0.0000462

AC:

AN:

151676

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000191

Gnomad4 NFE

AF:

0.0000590

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.0260

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Maple syrup urine disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over