rs2306478

Positions:

• chr4-103081991-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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]

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=-0.65).
• 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/exons	MANE	UniProt
BDH2	NM_020139.4	c.684+90G>A		intron_variant		ENST00000296424.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDH2	ENST00000296424.9	c.684+90G>A		intron_variant		1	NM_020139.4	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26763 AN: 152062 Hom.: 2506 Cov.: 33

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

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.291

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.176 AC: 26791 AN: 152180 Hom.: 2507 Cov.: 33 AF XY: 0.178 AC XY: 13254 AN XY: 74408

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.187

Alfa AF: 0.193 Hom.: 4039

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
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: rs2306478; hg19: chr4-104003148;