4-103083205-C-T

Position:

• chr4-103083205-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020139.4(BDH2):​c.533-276G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,224 control chromosomes in the GnomAD database, including 2,541 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 (2541 hom., cov: 33)
• Consequence: BDH2 NM_020139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00

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 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDH2	NM_020139.4	c.533-276G>A		intron_variant		ENST00000296424.9	NP_064524.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDH2	ENST00000296424.9	c.533-276G>A		intron_variant		1	NM_020139.4	ENSP00000296424.4

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26813 AN: 152106 Hom.: 2541 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.189

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.176 AC: 26840 AN: 152224 Hom.: 2541 Cov.: 33 AF XY: 0.179 AC XY: 13319 AN XY: 74424

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.187

Alfa AF: 0.197 Hom.: 4058

Bravo AF: 0.173

Asia WGS AF: 0.226 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.3
DANN	Benign	0.81

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

Other links and lift over

dbSNP: rs3775972; hg19: chr4-104004362;