chr3-197573140-C-T

Position:

• chr3-197573140-C-T

Variant summary

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

The NM_203315.3(BDH1):​c.-44+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,226 control chromosomes in the GnomAD database, including 2,185 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 0.16 (2185 hom., cov: 32)
  • Exomes 𝑓: 0.19 (0 hom.)
• Consequence: BDH1 NM_203315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDH1	XM_005269352.4	c.-75G>A		5_prime_UTR_variant	1/7		XP_005269409.1
BDH1	NM_203315.3	c.-44+41G>A		intron_variant			NP_976060.1
BDH1	XM_047448679.1	c.-2157+41G>A		intron_variant			XP_047304635.1
BDH1	XM_047448680.1	c.-3073+41G>A		intron_variant			XP_047304636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDH1	ENST00000358186.6	c.-44+41G>A		intron_variant		5		ENSP00000350914.2
BDH1	ENST00000431056.5	c.-44+41G>A		intron_variant		5		ENSP00000396149.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23780 AN: 152092 Hom.: 2186 Cov.: 32

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0866

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 3 AN XY: 12

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.143

GnomAD4 genome AF: 0.156 AC: 23776 AN: 152210 Hom.: 2185 Cov.: 32 AF XY: 0.151 AC XY: 11247 AN XY: 74420

Gnomad4 AFR AF: 0.0671

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.0862

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.175

Alfa AF: 0.185 Hom.: 2076

Bravo AF: 0.158

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.4
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2686110; hg19: chr3-197300011;