Variant 4-103095267-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_020139.4(BDH2):c.87A>C(p.Glu29Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00143 in 1,613,482 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 19 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 8 hom. )

Consequence

BDH2
NM_020139.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.85

Variant links:

Genes affected

BDH2 (HGNC:32389): (3-hydroxybutyrate dehydrogenase 2) Enables 3-hydroxybutyrate dehydrogenase activity and NAD binding activity. Involved in epithelial cell differentiation and fatty acid beta-oxidation. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

BDH2 links:

BDH2 (HGNC:):

BDH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012638837).

BP6

Variant 4-103095267-T-G is Benign according to our data. Variant chr4-103095267-T-G is described in ClinVar as [Benign]. Clinvar id is 788978.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00779 (1186/152308) while in subpopulation AFR AF= 0.0271 (1126/41568). AF 95% confidence interval is 0.0258. There are 19 homozygotes in gnomad4. There are 560 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDH2	NM_020139.4 linkuse as main transcript	c.87A>C	p.Glu29Asp	missense_variant	3/10	ENST00000296424.9	NP_064524.3	Q9BUT1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDH2	ENST00000296424.9 linkuse as main transcript	c.87A>C	p.Glu29Asp	missense_variant	3/10	1	NM_020139.4	ENSP00000296424.4		Q9BUT1-1

Frequencies

GnomAD3 genomes

AF:

0.00779

AC:

1185

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0271

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

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:

0.0000294

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00201

AC:

504

AN:

251208

Hom.:

AF XY:

0.00155

AC XY:

210

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.0284

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000769

AC:

1124

AN:

1461174

Hom.:

Cov.:

AF XY:

0.000664

AC XY:

483

AN XY:

726906

show subpopulations

Gnomad4 AFR exome

AF:

0.0290

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00779

AC:

1186

AN:

152308

Hom.:

Cov.:

AF XY:

0.00752

AC XY:

560

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0271

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00156

Hom.:

Bravo

AF:

0.00897

ESP6500AA

AF:

0.0291

AC:

128

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00268

AC:

326

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;.;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.99

D;D;D

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Uncertain

-0.085

MutationAssessor

Benign

1.2

L;.;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Uncertain

0.61

Sift

Uncertain

0.021

D;D;D

Sift4G

Uncertain

0.024

D;.;.

Polyphen

0.98

D;.;.

Vest4

0.82

MutPred

0.68

Gain of catalytic residue at E29 (P = 0.0632);Gain of catalytic residue at E29 (P = 0.0632);Gain of catalytic residue at E29 (P = 0.0632);

MVP

0.85

MPC

0.70

ClinPred

0.040

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.86

gMVP

0.70

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