Genetic Variant BDH1:p.Arg343His (chr3-197511899-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_203314.3(BDH1):c.1028G>A(p.Arg343His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,554,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

BDH1
NM_203314.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.768

Publications

1 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02584371).

BP6

Variant 3-197511899-C-T is Benign according to our data. Variant chr3-197511899-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2227005.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203314.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BDH1	NM_203314.3	MANE Select	c.1028G>A	p.Arg343His	missense	Exon 8 of 8	NP_976059.1	Q02338
BDH1	NM_004051.5		c.1028G>A	p.Arg343His	missense	Exon 7 of 7	NP_004042.1	Q02338
BDH1	NM_203315.3		c.1028G>A	p.Arg343His	missense	Exon 7 of 7	NP_976060.1	Q02338

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BDH1	ENST00000392379.6	TSL:5 MANE Select	c.1028G>A	p.Arg343His	missense	Exon 8 of 8	ENSP00000376184.1	Q02338
BDH1	ENST00000392378.6	TSL:1	c.1028G>A	p.Arg343His	missense	Exon 7 of 7	ENSP00000376183.2	Q02338
BDH1	ENST00000904000.1		c.1067G>A	p.Arg356His	missense	Exon 7 of 7	ENSP00000574059.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000240

AC:

AN:

208042

AF XY:

0.00000914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000422

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000214

AC:

AN:

1402640

Hom.:

Cov.:

AF XY:

0.0000232

AC XY:

AN XY:

689598

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32270

American (AMR)

AF:

0.00

AC:

AN:

39728

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21952

East Asian (EAS)

AF:

0.000204

AC:

AN:

39176

South Asian (SAS)

AF:

0.0000264

AC:

AN:

75654

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5466

European-Non Finnish (NFE)

AF:

0.0000167

AC:

AN:

1079616

Other (OTH)

AF:

0.0000346

AC:

AN:

57876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000329

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000332

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.37

CADD

Benign

3.8

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.28

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.28

M_CAP

Benign

0.068

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-1.7

PhyloP100

0.77

PrimateAI

Benign

0.21

PROVEAN

Benign

1.9

REVEL

Benign

0.16

Sift

Benign

0.54

Sift4G

Uncertain

0.034

Polyphen

0.0

Vest4

0.093

MVP

0.13

MPC

0.30

ClinPred

0.083

GERP RS

0.42

Varity_R

0.016

gMVP

0.66

Mutation Taster

=98/2

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over