7-27548587-G-A

Variant names:

• chr7-27548587-G-A
• rs10486547
• NM_152740.4:c.485-5487C>T

Variant summary

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

The NM_152740.4(HIBADH):​c.485-5487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 152,138 control chromosomes in the GnomAD database, including 151 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 0.038 (151 hom., cov: 31)
• Consequence: HIBADH NM_152740.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0778 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.485-5487C>T		intron	N/A	NP_689953.1
	HIBADH	NM_001430749.1		c.182-5487C>T		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.485-5487C>T		intron	N/A	ENSP00000265395.2
	HIBADH	ENST00000425715.1	TSL:2	c.311-5487C>T		intron	N/A	ENSP00000390205.1
	HIBADH	ENST00000428288.2	TSL:3	n.*204-5487C>T		intron	N/A	ENSP00000393365.1

Frequencies

GnomAD3 genomes AF: 0.0377 AC: 5733 AN: 152020 Hom.: 151 Cov.: 31

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.0747

Gnomad FIN AF: 0.00868

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0267

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

GnomAD4 genome AF: 0.0377 AC: 5735 AN: 152138 Hom.: 151 Cov.: 31 AF XY: 0.0374 AC XY: 2780 AN XY: 74370

African (AFR) AF: 0.0801 AC: 3323 AN: 41508

American (AMR) AF: 0.0181 AC: 276 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3470

East Asian (EAS) AF: 0.00908 AC: 47 AN: 5178

South Asian (SAS) AF: 0.0743 AC: 357 AN: 4804

European-Finnish (FIN) AF: 0.00868 AC: 92 AN: 10602

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0210 AC: 1429 AN: 67972

Other (OTH) AF: 0.0269 AC: 57 AN: 2116

Alfa AF: 0.0282 Hom.: 130

Bravo AF: 0.0371

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.52
PhyloP100		-0.96
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: rs10486547; hg19: chr7-27588206;