rs1050119

Variant names:

• chr3-197511616-C-T
• rs1050119
• NM_203314.3:c.*279G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

BDH1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203314.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDH1	NM_203314.3	MANE Select	c.*279G>A		3_prime_UTR	Exon 8 of 8	NP_976059.1
	BDH1	NM_004051.5		c.*279G>A		3_prime_UTR	Exon 7 of 7	NP_004042.1
	BDH1	NM_203315.3		c.*279G>A		3_prime_UTR	Exon 7 of 7	NP_976060.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDH1	ENST00000392379.6	TSL:5 MANE Select	c.*279G>A		3_prime_UTR	Exon 8 of 8	ENSP00000376184.1
	BDH1	ENST00000392378.6	TSL:1	c.*279G>A		3_prime_UTR	Exon 7 of 7	ENSP00000376183.2
	BDH1	ENST00000651856.1		n.*4569G>A		non_coding_transcript_exon	Exon 12 of 12	ENSP00000498996.1

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

African (AFR) AF: 0.0661 AC: 488 AN: 7384

American (AMR) AF: 0.164 AC: 1634 AN: 9960

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 2504 AN: 9216

East Asian (EAS) AF: 0.000304 AC: 7 AN: 23062

South Asian (SAS) AF: 0.0600 AC: 311 AN: 5180

European-Finnish (FIN) AF: 0.317 AC: 6403 AN: 20208

Middle Eastern (MID) AF: 0.151 AC: 202 AN: 1342

European-Non Finnish (NFE) AF: 0.293 AC: 47825 AN: 163150

Other (OTH) AF: 0.238 AC: 4040 AN: 16982

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

African (AFR) AF: 0.0659 AC: 2736 AN: 41524

American (AMR) AF: 0.176 AC: 2693 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 942 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.0699 AC: 337 AN: 4820

European-Finnish (FIN) AF: 0.323 AC: 3413 AN: 10582

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20541 AN: 67986

Other (OTH) AF: 0.222 AC: 468 AN: 2110

Alfa AF: 0.222 Hom.: 3232

Bravo AF: 0.195

Asia WGS AF: 0.0430 AC: 153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.78
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1050119; hg19: chr3-197238487;