rs3791789

Variant names:

• chr2-190220095-T-C
• rs3791789
• NM_014362.4:c.892-7020A>G

Variant summary

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

The NM_014362.4(HIBCH):​c.892-7020A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,092 control chromosomes in the GnomAD database, including 8,258 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 0.31 (8258 hom., cov: 32)
• Consequence: HIBCH NM_014362.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIBCH	NM_014362.4	MANE Select	c.892-7020A>G		intron	N/A	NP_055177.2
	HIBCH	NM_198047.3		c.892-7020A>G		intron	N/A	NP_932164.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIBCH	ENST00000359678.10	TSL:1 MANE Select	c.892-7020A>G		intron	N/A	ENSP00000352706.5
	HIBCH	ENST00000392332.7	TSL:1	c.892-7020A>G		intron	N/A	ENSP00000376144.3
	HIBCH	ENST00000870406.1		c.892-7020A>G		intron	N/A	ENSP00000540465.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46811 AN: 151972 Hom.: 8233 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.308 AC: 46890 AN: 152092 Hom.: 8258 Cov.: 32 AF XY: 0.303 AC XY: 22556 AN XY: 74368

African (AFR) AF: 0.457 AC: 18959 AN: 41454

American (AMR) AF: 0.282 AC: 4311 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3470

East Asian (EAS) AF: 0.474 AC: 2456 AN: 5180

South Asian (SAS) AF: 0.246 AC: 1187 AN: 4822

European-Finnish (FIN) AF: 0.132 AC: 1401 AN: 10598

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16867 AN: 67988

Other (OTH) AF: 0.320 AC: 676 AN: 2110

Alfa AF: 0.273 Hom.: 1115

Bravo AF: 0.329

Asia WGS AF: 0.352 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.8
DANN	Benign	0.66
PhyloP100		0.14
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: rs3791789; hg19: chr2-191084821;