6-80203260-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_183050.4(BCKDHB):c.951+48C>T variant causes a intron 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_183050.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.162

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

maple syrup urine disease type 1B
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, G2P, Myriad Women’s Health
maple syrup urine disease
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
classic maple syrup urine disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
intermediate maple syrup urine disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
intermittent maple syrup urine disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
thiamine-responsive maple syrup urine disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BCKDHB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
BCKDHB	NM_183050.4 link	c.951+48C>T		intron_variant	Intron 8 of 9	ENST00000320393.9	NP_898871.1	P21953-1A0A140VKB3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BCKDHB	ENST00000320393.9 link	c.951+48C>T	intron_variant	Intron 8 of 9	1	NM_183050.4	ENSP00000318351.5	P21953-1
BCKDHB	ENST00000356489.9 link	c.951+48C>T	intron_variant	Intron 8 of 10	1		ENSP00000348880.5	P21953-1
BCKDHB	ENST00000468520.1 link	n.111+48C>T	intron_variant	Intron 1 of 2	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

GnomAD2 exomes

AF:

0.0781

AC:

19391

AN:

248228

AF XY:

0.0854

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 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

African (AFR)

AF:

0.110

AC:

2967

AN:

26982

American (AMR)

AF:

0.0302

AC:

1334

AN:

44134

Ashkenazi Jewish (ASJ)

AF:

0.0638

AC:

1534

AN:

24052

East Asian (EAS)

AF:

0.155

AC:

5887

AN:

38098

South Asian (SAS)

AF:

0.229

AC:

18219

AN:

79434

European-Finnish (FIN)

AF:

0.0383

AC:

2031

AN:

53040

Middle Eastern (MID)

AF:

0.0860

AC:

443

AN:

5154

European-Non Finnish (NFE)

AF:

0.0426

AC:

34706

AN:

814602

Other (OTH)

AF:

0.0691

AC:

3436

AN:

49718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3271

6541

9812

13082

16353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1284

2568

3852

5136

6420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0719

AC:

10926

AN:

151990

Hom.:

584

Cov.:

AF XY:

0.0743

AC XY:

5517

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.106

AC:

4389

AN:

41456

American (AMR)

AF:

0.0387

AC:

591

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0680

AC:

236

AN:

3470

East Asian (EAS)

AF:

0.137

AC:

710

AN:

5170

South Asian (SAS)

AF:

0.237

AC:

1140

AN:

4820

European-Finnish (FIN)

AF:

0.0384

AC:

406

AN:

10586

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0467

AC:

3171

AN:

67916

Other (OTH)

AF:

0.0795

AC:

168

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

509

1018

1528

2037

2546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0457

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

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 23, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Maple syrup urine disease

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.9

(source)

DANN

Benign

0.45

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over