rs2686110

chr3-197573140-C-Achr3-197573140-C-Gchr3-197573140-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The XM_005269352.4(BDH1):c.-75G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 152,236 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BDH1 XM_005269352.4 5_prime_UTR
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDH1	ENST00000358186.6	c.-44+41G>T		intron_variant		5		P1
BDH1	ENST00000431056.5	c.-44+41G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74436

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	2.9
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;