dbSNP rs2306478: BDH2:c.684+90G>A (chr4-103081991-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020139.4(BDH2):c.684+90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,072,202 control chromosomes in the GnomAD database, including 20,643 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2507 hom., cov: 33)

Exomes 𝑓: 0.20 ( 18136 hom. )

Consequence

BDH2
NM_020139.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.02

Publications

4 publications found

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:

SLC9B2 (HGNC:25143): (solute carrier family 9 member B2) Sodium hydrogen antiporters, such as NHEDC2, convert the proton motive force established by the respiratory chain or the F1F0 mitochondrial ATPase into sodium gradients that drive other energy-requiring processes, transduce environmental signals into cell responses, or function in drug efflux (Xiang et al., 2007 [PubMed 18000046]).[supplied by OMIM, Mar 2008]

SLC9B2 links:

ENSG00000299907 (HGNC:):

ENSG00000299907 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDH2	NM_020139.4 link	c.684+90G>A		intron_variant	Intron 9 of 9	ENST00000296424.9	NP_064524.3	Q9BUT1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDH2	ENST00000296424.9 link	c.684+90G>A		intron_variant	Intron 9 of 9	1	NM_020139.4	ENSP00000296424.4		Q9BUT1-1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26763

AN:

152062

Hom.:

2506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.189

GnomAD4 exome

AF:

0.196

AC:

180440

AN:

920022

Hom.:

18136

AF XY:

0.200

AC XY:

94442

AN XY:

471640

show subpopulations

African (AFR)

AF:

0.131

AC:

2971

AN:

22646

American (AMR)

AF:

0.206

AC:

7447

AN:

36220

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

4643

AN:

21424

East Asian (EAS)

AF:

0.113

AC:

3958

AN:

35162

South Asian (SAS)

AF:

0.291

AC:

19942

AN:

68570

European-Finnish (FIN)

AF:

0.160

AC:

7904

AN:

49476

Middle Eastern (MID)

AF:

0.258

AC:

882

AN:

3422

European-Non Finnish (NFE)

AF:

0.194

AC:

124036

AN:

640862

Other (OTH)

AF:

0.205

AC:

8657

AN:

42240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

7201

14401

21602

28802

36003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3448

6896

10344

13792

17240

<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:

0.176

AC:

26791

AN:

152180

Hom.:

2507

Cov.:

AF XY:

0.178

AC XY:

13254

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.127

AC:

5282

AN:

41516

American (AMR)

AF:

0.215

AC:

3283

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

737

AN:

3468

East Asian (EAS)

AF:

0.139

AC:

719

AN:

5178

South Asian (SAS)

AF:

0.302

AC:

1456

AN:

4828

European-Finnish (FIN)

AF:

0.158

AC:

1670

AN:

10574

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.192

AC:

13036

AN:

68000

Other (OTH)

AF:

0.187

AC:

395

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1136

2272

3408

4544

5680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.191

Hom.:

5767

Bravo

AF:

0.174

Asia WGS

AF:

0.227

AC:

789

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.28

(source)

DANN

Benign

0.81

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over