rs1404282

Variant names:

• chr7-27545832-A-C
• rs1404282
• NM_152740.4:c.485-2732T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

HIBADH Gene-Disease associations (from GenCC):

• 3-hydroxyisobutyric aciduria

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• inborn organic aciduria

  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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152740.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIBADH	NM_152740.4	MANE Select	c.485-2732T>G		intron	N/A	NP_689953.1
	HIBADH	NM_001430749.1		c.182-2732T>G		intron	N/A	NP_001417678.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIBADH	ENST00000265395.7	TSL:1 MANE Select	c.485-2732T>G		intron	N/A	ENSP00000265395.2
	HIBADH	ENST00000425715.1	TSL:2	c.311-2732T>G		intron	N/A	ENSP00000390205.1
	HIBADH	ENST00000428288.2	TSL:3	n.*204-2732T>G		intron	N/A	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

African (AFR) AF: 0.900 AC: 37364 AN: 41518

American (AMR) AF: 0.786 AC: 12013 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2866 AN: 3472

East Asian (EAS) AF: 0.971 AC: 5014 AN: 5166

South Asian (SAS) AF: 0.799 AC: 3848 AN: 4818

European-Finnish (FIN) AF: 0.767 AC: 8116 AN: 10578

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49461 AN: 68006

Other (OTH) AF: 0.797 AC: 1684 AN: 2114

Alfa AF: 0.749 Hom.: 21022

Bravo AF: 0.807

Asia WGS AF: 0.896 AC: 3113 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.65
DANN	Benign	0.46
PhyloP100		-1.2
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: rs1404282; hg19: chr7-27585451;