rs1050119

Positions:

• chr3-197511616-C-T

Variant summary

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

The NM_203314.3(BDH1):​c.*279G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 408,630 control chromosomes in the GnomAD database, including 13,591 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 0.21 (4257 hom., cov: 33)
  • Exomes 𝑓: 0.25 (9334 hom.)
• Consequence: BDH1 NM_203314.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDH1	NM_203314.3	c.*279G>A		3_prime_UTR_variant	8/8	ENST00000392379.6	NP_976059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDH1	ENST00000392379.6	c.*279G>A		3_prime_UTR_variant	8/8	5	NM_203314.3	ENSP00000376184	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31479 AN: 152028 Hom.: 4256 Cov.: 33

Gnomad AFR AF: 0.0659

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0703

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.247 AC: 63414 AN: 256484 Hom.: 9334 Cov.: 0 AF XY: 0.249 AC XY: 32390 AN XY: 130298

Gnomad4 AFR exome AF: 0.0661

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.000304

Gnomad4 SAS exome AF: 0.0600

Gnomad4 FIN exome AF: 0.317

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.207 AC: 31480 AN: 152146 Hom.: 4257 Cov.: 33 AF XY: 0.203 AC XY: 15123 AN XY: 74364

Gnomad4 AFR AF: 0.0659

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0699

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.222

Alfa AF: 0.260 Hom.: 2187

Bravo AF: 0.195

Asia WGS AF: 0.0430 AC: 153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.78

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: rs1050119; hg19: chr3-197238487;