Variant 3-197511986-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP3BP4_ModerateBP6_ModerateBS2

The NM_203314.3(BDH1):c.941G>A(p.Arg314His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,611,480 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 5 hom. )

Consequence

BDH1
NM_203314.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.91

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.21549278).

BP6

Variant 3-197511986-C-T is Benign according to our data. Variant chr3-197511986-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3052892.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDH1	NM_203314.3 linkuse as main transcript	c.941G>A	p.Arg314His	missense_variant	8/8	ENST00000392379.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDH1	ENST00000392379.6 linkuse as main transcript	c.941G>A	p.Arg314His	missense_variant	8/8	5	NM_203314.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

171

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00228

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000958

AC:

238

AN:

248542

Hom.:

AF XY:

0.000947

AC XY:

127

AN XY:

134072

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000328

Gnomad NFE exome

AF:

0.00194

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00148

AC:

2164

AN:

1459374

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

1049

AN XY:

725756

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.000155

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000338

Gnomad4 NFE exome

AF:

0.00187

Gnomad4 OTH exome

AF:

0.000663

GnomAD4 genome

AF:

0.00112

AC:

171

AN:

152106

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.000242

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00228

Gnomad4 OTH

AF:

0.000959

Alfa

AF:

0.00159

Hom.:

Bravo

AF:

0.00101

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00116

AC:

141

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

BDH1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 14, 2022

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

0.0061

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.71

D;D;D;T

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Uncertain

0.95

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Pathogenic

0.96

MutationAssessor

Pathogenic

2.9

M;M;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-4.8

D;D;D;D

REVEL

Pathogenic

0.75

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.71

MVP

1.0

MPC

0.99

ClinPred

0.22

GERP RS

5.8

Varity_R

0.71

gMVP

0.88

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