Variant rs73479953 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000320393.9(BCKDHB):c.344-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 1,583,272 control chromosomes in the GnomAD database, including 5,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 580 hom., cov: 32)

Exomes 𝑓: 0.059 ( 4475 hom. )

Consequence

BCKDHB
ENST00000320393.9 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.74

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 6-80167654-C-T is Benign according to our data. Variant chr6-80167654-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 96581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCKDHB	NM_183050.4 linkuse as main transcript	c.344-24C>T		intron_variant		ENST00000320393.9	NP_898871.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
BCKDHB	ENST00000320393.9 linkuse as main transcript	c.344-24C>T	intron_variant	1	NM_183050.4	ENSP00000318351	P1	P21953-1
BCKDHB	ENST00000356489.9 linkuse as main transcript	c.344-24C>T	intron_variant	1		ENSP00000348880	P1	P21953-1
BCKDHB	ENST00000369760.8 linkuse as main transcript	c.344-24C>T	intron_variant	3		ENSP00000358775		P21953-2

Frequencies

GnomAD3 genomes

AF:

0.0717

AC:

10905

AN:

152046

Hom.:

581

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.0384

Gnomad ASJ

AF:

0.0678

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.0384

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0467

Gnomad OTH

AF:

0.0756

GnomAD3 exomes

AF:

0.0777

AC:

19425

AN:

250108

Hom.:

1386

AF XY:

0.0850

AC XY:

11501

AN XY:

135276

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.0284

Gnomad ASJ exome

AF:

0.0600

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.236

Gnomad FIN exome

AF:

0.0398

Gnomad NFE exome

AF:

0.0450

Gnomad OTH exome

AF:

0.0658

GnomAD4 exome

AF:

0.0594

AC:

84971

AN:

1431106

Hom.:

4475

Cov.:

AF XY:

0.0647

AC XY:

46151

AN XY:

713680

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.0300

Gnomad4 ASJ exome

AF:

0.0643

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.0379

Gnomad4 NFE exome

AF:

0.0424

Gnomad4 OTH exome

AF:

0.0695

GnomAD4 genome

AF:

0.0717

AC:

10915

AN:

152166

Hom.:

580

Cov.:

AF XY:

0.0741

AC XY:

5514

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.0384

Gnomad4 ASJ

AF:

0.0678

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.237

Gnomad4 FIN

AF:

0.0384

Gnomad4 NFE

AF:

0.0467

Gnomad4 OTH

AF:

0.0795

Alfa

AF:

0.0580

Hom.:

Bravo

AF:

0.0689

Asia WGS

AF:

0.191

AC:

666

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 23, 2013	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Maple syrup urine disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.30

DANN

Benign

0.26

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