chr2-190318235-C-A

Variant names:

• chr2-190318235-C-A
• rs291465
• NM_014362.4:c.35+1481G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014362.4(HIBCH):​c.35+1481G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 26)
  • Failed GnomAD Quality Control
• Consequence: HIBCH NM_014362.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• Publications: 1 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: Orphanet, Ambry Genetics, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), ClinGen
• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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.35+1481G>T		intron	N/A	NP_055177.2
	HIBCH	NM_198047.3		c.35+1481G>T		intron	N/A	NP_932164.1	Q6NVY1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIBCH	ENST00000359678.10	TSL:1 MANE Select	c.35+1481G>T		intron	N/A	ENSP00000352706.5	Q6NVY1-1
	HIBCH	ENST00000392332.7	TSL:1	c.35+1481G>T		intron	N/A	ENSP00000376144.3	Q6NVY1-2
	HIBCH	ENST00000870406.1		c.35+1481G>T		intron	N/A	ENSP00000540465.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151086 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151190 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 73766

African (AFR) AF: 0.00 AC: 0 AN: 41112

American (AMR) AF: 0.00 AC: 0 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67868

Other (OTH) AF: 0.00 AC: 0 AN: 2102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.3
DANN	Benign	0.089
PhyloP100		0.26

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: rs291465; hg19: chr2-191182961;