4-103083205-C-T

Variant names:

• chr4-103083205-C-T
• rs3775972
• NM_020139.4:c.533-276G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020139.4(BDH2):​c.533-276G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,224 control chromosomes in the GnomAD database, including 2,541 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 0.18 (2541 hom., cov: 33)
• Consequence: BDH2 NM_020139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 7 publications found

Genes affected

BDH2 (HGNC:32389): (3-hydroxybutyrate dehydrogenase 2) Enables 3-hydroxybutyrate dehydrogenase activity and NAD binding activity. Involved in epithelial cell differentiation and fatty acid beta-oxidation. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

SLC9B2 (HGNC:25143): (solute carrier family 9 member B2) Sodium hydrogen antiporters, such as NHEDC2, convert the proton motive force established by the respiratory chain or the F1F0 mitochondrial ATPase into sodium gradients that drive other energy-requiring processes, transduce environmental signals into cell responses, or function in drug efflux (Xiang et al., 2007 [PubMed 18000046]).[supplied by OMIM, Mar 2008]

ENSG00000299907 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDH2	NM_020139.4	c.533-276G>A		intron_variant	Intron 7 of 9	ENST00000296424.9	NP_064524.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDH2	ENST00000296424.9	c.533-276G>A		intron_variant	Intron 7 of 9	1	NM_020139.4	ENSP00000296424.4

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26813 AN: 152106 Hom.: 2541 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.176 AC: 26840 AN: 152224 Hom.: 2541 Cov.: 33 AF XY: 0.179 AC XY: 13319 AN XY: 74424

African (AFR) AF: 0.119 AC: 4960 AN: 41544

American (AMR) AF: 0.215 AC: 3290 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3468

East Asian (EAS) AF: 0.139 AC: 717 AN: 5172

South Asian (SAS) AF: 0.303 AC: 1465 AN: 4828

European-Finnish (FIN) AF: 0.167 AC: 1770 AN: 10588

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13235 AN: 68004

Other (OTH) AF: 0.187 AC: 396 AN: 2114

Alfa AF: 0.194 Hom.: 5334

Bravo AF: 0.173

Asia WGS AF: 0.226 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.3
DANN	Benign	0.81
PhyloP100		1.0
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: rs3775972; hg19: chr4-104004362;