NM_014362.4:c.750+1357A>C

Variant names:

• chr2-190248283-T-G
• rs2562796
• NM_014362.4:c.750+1357A>C

Variant summary

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

The NM_014362.4(HIBCH):​c.750+1357A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,062 control chromosomes in the GnomAD database, including 7,508 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 0.30 (7508 hom., cov: 32)
• Consequence: HIBCH NM_014362.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• Publications: 11 publications found

Genes affected

HIBCH (HGNC:4908): (3-hydroxyisobutyryl-CoA hydrolase) This gene encodes the enzyme responsible for hydrolysis of both HIBYL-CoA and beta-hydroxypropionyl-CoA. Mutations in this gene have been associated with 3-hyroxyisobutyryl-CoA hydrolase deficiency. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

HIBCH Gene-Disease associations (from GenCC):

• 3-hydroxyisobutyryl-CoA hydrolase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014362.4. 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
	HIBCH	NM_014362.4	MANE Select	c.750+1357A>C		intron	N/A	NP_055177.2
	HIBCH	NM_198047.3		c.750+1357A>C		intron	N/A	NP_932164.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIBCH	ENST00000359678.10	TSL:1 MANE Select	c.750+1357A>C		intron	N/A	ENSP00000352706.5
	HIBCH	ENST00000392332.7	TSL:1	c.750+1357A>C		intron	N/A	ENSP00000376144.3
	HIBCH	ENST00000410045.5	TSL:3	c.81+1357A>C		intron	N/A	ENSP00000386274.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45071 AN: 151944 Hom.: 7486 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.297 AC: 45139 AN: 152062 Hom.: 7508 Cov.: 32 AF XY: 0.292 AC XY: 21685 AN XY: 74342

African (AFR) AF: 0.422 AC: 17461 AN: 41418

American (AMR) AF: 0.276 AC: 4217 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 755 AN: 3466

East Asian (EAS) AF: 0.455 AC: 2355 AN: 5172

South Asian (SAS) AF: 0.246 AC: 1184 AN: 4812

European-Finnish (FIN) AF: 0.132 AC: 1401 AN: 10594

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16839 AN: 67986

Other (OTH) AF: 0.310 AC: 656 AN: 2116

Alfa AF: 0.266 Hom.: 1022

Bravo AF: 0.315

Asia WGS AF: 0.346 AC: 1201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		-0.57
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: rs2562796; hg19: chr2-191113009;