rs1404282

Positions:

• chr7-27545832-A-C
• chr7-27545832-A-G

Variant summary

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

The NM_152740.4(HIBADH):​c.485-2732T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,156 control chromosomes in the GnomAD database, including 48,772 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 0.80 (48772 hom., cov: 32)
• Consequence: HIBADH NM_152740.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

Genes affected

HIBADH (HGNC:4907): (3-hydroxyisobutyrate dehydrogenase) This gene encodes a mitochondrial 3-hydroxyisobutyrate dehydrogenase enzyme. The encoded protein plays a critical role in the catabolism of L-valine by catalyzing the oxidation of 3-hydroxyisobutyrate to methylmalonate semialdehyde. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIBADH	NM_152740.4	c.485-2732T>G		intron_variant		ENST00000265395.7	NP_689953.1
HIBADH	XM_047419834.1	c.182-2732T>G		intron_variant			XP_047275790.1
HIBADH	XM_047419835.1	c.182-2732T>G		intron_variant			XP_047275791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIBADH	ENST00000265395.7	c.485-2732T>G		intron_variant		1	NM_152740.4	ENSP00000265395.2
HIBADH	ENST00000425715.1	c.311-2732T>G		intron_variant		2		ENSP00000390205.1
HIBADH	ENST00000428288.2	n.*204-2732T>G		intron_variant		3		ENSP00000393365.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121151 AN: 152038 Hom.: 48718 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.797

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

GnomAD4 genome AF: 0.797 AC: 121262 AN: 152156 Hom.: 48772 Cov.: 32 AF XY: 0.799 AC XY: 59401 AN XY: 74368

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.971

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.797

Alfa AF: 0.751 Hom.: 12447

Bravo AF: 0.807

Asia WGS AF: 0.896 AC: 3113 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.65
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs1404282; hg19: chr7-27585451;