3-197545586-A-T

Variant names:

• chr3-197545586-A-T
• rs13097456
• NM_203314.3:c.83+775T>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.83+775T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,154 control chromosomes in the GnomAD database, including 5,291 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 0.26 (5291 hom., cov: 33)
• Consequence: BDH1 NM_203314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDH1	NM_203314.3	c.83+775T>A		intron_variant	Intron 3 of 7	ENST00000392379.6	NP_976059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDH1	ENST00000392379.6	c.83+775T>A		intron_variant	Intron 3 of 7	5	NM_203314.3	ENSP00000376184.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39010 AN: 152036 Hom.: 5291 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.257 AC: 39031 AN: 152154 Hom.: 5291 Cov.: 33 AF XY: 0.253 AC XY: 18828 AN XY: 74400

African (AFR) AF: 0.233 AC: 9682 AN: 41496

American (AMR) AF: 0.241 AC: 3694 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1009 AN: 3472

East Asian (EAS) AF: 0.102 AC: 528 AN: 5186

South Asian (SAS) AF: 0.215 AC: 1039 AN: 4834

European-Finnish (FIN) AF: 0.297 AC: 3147 AN: 10586

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 18998 AN: 67966

Other (OTH) AF: 0.277 AC: 584 AN: 2112

Alfa AF: 0.190 Hom.: 480

Bravo AF: 0.250

Asia WGS AF: 0.186 AC: 645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.45
PhyloP100		-0.43
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: rs13097456; hg19: chr3-197272457;