Variant chr6-80203260-C-T 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 NM_001424044.1(BCKDHB):c.*42C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 1,287,204 control chromosomes in the GnomAD database, including 4,559 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 ( 584 hom., cov: 32)

Exomes 𝑓: 0.062 ( 3975 hom. )

Consequence

BCKDHB
NM_001424044.1 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.162

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 6-80203260-C-T is Benign according to our data. Variant chr6-80203260-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 96619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 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.951+48C>T		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.951+48C>T	intron_variant	1	NM_183050.4	ENSP00000318351.5	P21953-1
BCKDHB	ENST00000356489.9 linkuse as main transcript	c.951+48C>T	intron_variant	1		ENSP00000348880.5	P21953-1
BCKDHB	ENST00000468520.1 linkuse as main transcript	n.111+48C>T	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.0719

AC:

10916

AN:

151874

Hom.:

585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.0388

Gnomad ASJ

AF:

0.0680

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.0384

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0467

Gnomad OTH

AF:

0.0756

GnomAD3 exomes

AF:

0.0781

AC:

19391

AN:

248228

Hom.:

1373

AF XY:

0.0854

AC XY:

11457

AN XY:

134210

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.0289

Gnomad ASJ exome

AF:

0.0598

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.236

Gnomad FIN exome

AF:

0.0403

Gnomad NFE exome

AF:

0.0453

Gnomad OTH exome

AF:

0.0666

GnomAD4 exome

AF:

0.0622

AC:

70557

AN:

1135214

Hom.:

3975

Cov.:

AF XY:

0.0682

AC XY:

39558

AN XY:

580082

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.0302

Gnomad4 ASJ exome

AF:

0.0638

Gnomad4 EAS exome

AF:

0.155

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.0383

Gnomad4 NFE exome

AF:

0.0426

Gnomad4 OTH exome

AF:

0.0691

GnomAD4 genome

AF:

0.0719

AC:

10926

AN:

151990

Hom.:

584

Cov.:

AF XY:

0.0743

AC XY:

5517

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.0387

Gnomad4 ASJ

AF:

0.0680

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:

0.0409

Hom.:

Bravo

AF:

0.0689

Asia WGS

AF:

0.191

AC:

667

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

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

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

-0.86

CADD

Benign

5.9

DANN

Benign

0.45

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