chr6-80127536-G-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.197-11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,555,556 control chromosomes in the GnomAD database, including 143,841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16096 hom., cov: 32)

Exomes 𝑓: 0.46 ( 127745 hom. )

Consequence

BCKDHB
NM_183050.4 intron

Scores

Splicing: ADA: 0.00001270

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.218

Publications

8 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=-0.85).

BP6

Variant 6-80127536-G-T is Benign according to our data. Variant chr6-80127536-G-T is described in ClinVar as Benign. ClinVar VariationId is 96572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCKDHB	NM_183050.4 link	c.197-11G>T		intron_variant	Intron 1 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.197-11G>T	intron_variant	Intron 1 of 9	1	NM_183050.4	ENSP00000318351.5	P21953-1
BCKDHB	ENST00000356489.9 link	c.197-11G>T	intron_variant	Intron 1 of 10	1		ENSP00000348880.5	P21953-1
BCKDHB	ENST00000369760.8 link	c.197-11G>T	intron_variant	Intron 1 of 5	3		ENSP00000358775.4	P21953-2
BCKDHB	ENST00000486968.1 link	n.111-11G>T	intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.441

AC:

66288

AN:

150356

Hom.:

16077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.542

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.546

Gnomad EAS

AF:

0.696

Gnomad SAS

AF:

0.662

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.571

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.491

GnomAD2 exomes

AF:

0.460

AC:

107851

AN:

234524

AF XY:

0.461

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.562

Gnomad ASJ exome

AF:

0.473

Gnomad EAS exome

AF:

0.572

Gnomad FIN exome

AF:

0.445

Gnomad NFE exome

AF:

0.436

Gnomad OTH exome

AF:

0.476

GnomAD4 exome

AF:

0.461

AC:

648014

AN:

1405096

Hom.:

127745

Cov.:

AF XY:

0.464

AC XY:

324403

AN XY:

699316

show subpopulations

African (AFR)

AF:

0.213

AC:

6817

AN:

31994

American (AMR)

AF:

0.595

AC:

25322

AN:

42544

Ashkenazi Jewish (ASJ)

AF:

0.497

AC:

12521

AN:

25170

East Asian (EAS)

AF:

0.600

AC:

22419

AN:

37382

South Asian (SAS)

AF:

0.559

AC:

45846

AN:

82068

European-Finnish (FIN)

AF:

0.457

AC:

23692

AN:

51812

Middle Eastern (MID)

AF:

0.543

AC:

3026

AN:

5572

European-Non Finnish (NFE)

AF:

0.449

AC:

481186

AN:

1070642

Other (OTH)

AF:

0.469

AC:

27185

AN:

57912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

16338

32676

49015

65353

81691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15112

30224

45336

60448

75560

<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:

0.441

AC:

66329

AN:

150460

Hom.:

16096

Cov.:

AF XY:

0.449

AC XY:

32985

AN XY:

73460

show subpopulations

African (AFR)

AF:

0.226

AC:

9253

AN:

40902

American (AMR)

AF:

0.598

AC:

9044

AN:

15126

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

1887

AN:

3454

East Asian (EAS)

AF:

0.695

AC:

3578

AN:

5146

South Asian (SAS)

AF:

0.663

AC:

3178

AN:

4790

European-Finnish (FIN)

AF:

0.491

AC:

5001

AN:

10188

Middle Eastern (MID)

AF:

0.580

AC:

166

AN:

286

European-Non Finnish (NFE)

AF:

0.484

AC:

32695

AN:

67570

Other (OTH)

AF:

0.495

AC:

1034

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1781

3562

5343

7124

8905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<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:

0.176

Hom.:

1176

Bravo

AF:

0.435

Asia WGS

AF:

0.653

AC:

2269

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Mar 13, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 25, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Maple syrup urine disease

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.85

CADD

Benign

0.28

(source)

DANN

Benign

0.56

PhyloP100

-0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000013

dbscSNV1_RF

Benign

0.0

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

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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