chr3-197514412-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_203314.3(BDH1):c.414G>A(p.Met138Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 1,604,778 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

BDH1
NM_203314.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.33

Publications

4 publications found

Variant links:

Genes affected

BDH1 (HGNC:1027): (3-hydroxybutyrate dehydrogenase 1) This gene encodes a member of the short-chain dehydrogenase/reductase gene family. The encoded protein forms a homotetrameric lipid-requiring enzyme of the mitochondrial membrane and has a specific requirement for phosphatidylcholine for optimal enzymatic activity. The encoded protein catalyzes the interconversion of acetoacetate and (R)-3-hydroxybutyrate, the two major ketone bodies produced during fatty acid catabolism. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

BDH1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

BDH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011364222).

BP6

Variant 3-197514412-C-T is Benign according to our data. Variant chr3-197514412-C-T is described in ClinVar as Benign. ClinVar VariationId is 720182.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDH1	NM_203314.3 link	c.414G>A	p.Met138Ile	missense_variant	Exon 7 of 8	ENST00000392379.6	NP_976059.1	Q02338A0A384MTY4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDH1	ENST00000392379.6 link	c.414G>A	p.Met138Ile	missense_variant	Exon 7 of 8	5	NM_203314.3	ENSP00000376184.1		Q02338

Frequencies

GnomAD3 genomes

AF:

0.00224

AC:

341

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00794

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000551

AC:

134

AN:

243196

AF XY:

0.000328

show subpopulations

Gnomad AFR exome

AF:

0.00775

Gnomad AMR exome

AF:

0.000178

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000509

GnomAD4 exome

AF:

0.000232

AC:

337

AN:

1452470

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

147

AN XY:

721616

show subpopulations

African (AFR)

AF:

0.00918

AC:

306

AN:

33328

American (AMR)

AF:

0.000113

AC:

AN:

44160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25492

East Asian (EAS)

AF:

0.00

AC:

AN:

39374

South Asian (SAS)

AF:

0.00

AC:

AN:

84620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53158

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1106620

Other (OTH)

AF:

0.000350

AC:

AN:

59990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00225

AC:

342

AN:

152308

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00794

AC:

330

AN:

41574

American (AMR)

AF:

0.000523

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000802

Hom.:

Bravo

AF:

0.00269

ESP6500AA

AF:

0.00885

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000708

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

BDH1-related disorder

Benign:1

Jan 20, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Aug 15, 2018

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

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

T;T;T;T;.;T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.83

MetaRNN

Benign

0.011

T;T;T;T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

-1.8

N;N;N;.;.;.;.

PhyloP100

1.3

PrimateAI

Benign

0.41

PROVEAN

Benign

0.020

N;N;N;N;N;N;N

REVEL

Benign

0.29

Sift

Benign

0.064

T;T;T;D;T;D;D

Sift4G

Uncertain

0.026

D;D;D;D;D;.;.

Polyphen

0.0

B;B;B;.;.;.;.

Vest4

0.48

MutPred

0.70

Loss of disorder (P = 0.1014);Loss of disorder (P = 0.1014);Loss of disorder (P = 0.1014);.;.;.;Loss of disorder (P = 0.1014);

MVP

0.66

MPC

0.28

ClinPred

0.025

GERP RS

4.1

PromoterAI

-0.012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.52

Mutation Taster

=94/6

polymorphism

(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

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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