chr2-190318235-C-G

Variant names:

• chr2-190318235-C-G
• rs291465
• NM_014362.4:c.35+1481G>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.35+1481G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.973 in 151,186 control chromosomes in the GnomAD database, including 71,557 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 0.97 (71557 hom., cov: 26)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.973 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.35+1481G>C		intron	N/A	NP_055177.2
	HIBCH	NM_198047.3		c.35+1481G>C		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>C		intron	N/A	ENSP00000352706.5	Q6NVY1-1
	HIBCH	ENST00000392332.7	TSL:1	c.35+1481G>C		intron	N/A	ENSP00000376144.3	Q6NVY1-2
	HIBCH	ENST00000870406.1		c.35+1481G>C		intron	N/A	ENSP00000540465.1

Frequencies

GnomAD3 genomes AF: 0.973 AC: 146944 AN: 151082 Hom.: 71512 Cov.: 26

Gnomad AFR AF: 0.974

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.979

Gnomad OTH AF: 0.964

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

GnomAD4 genome AF: 0.973 AC: 147040 AN: 151186 Hom.: 71557 Cov.: 26 AF XY: 0.971 AC XY: 71651 AN XY: 73764

African (AFR) AF: 0.974 AC: 40031 AN: 41108

American (AMR) AF: 0.985 AC: 14991 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.980 AC: 3399 AN: 3468

East Asian (EAS) AF: 0.850 AC: 4346 AN: 5114

South Asian (SAS) AF: 0.934 AC: 4462 AN: 4778

European-Finnish (FIN) AF: 0.985 AC: 10163 AN: 10322

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.979 AC: 66437 AN: 67868

Other (OTH) AF: 0.965 AC: 2026 AN: 2100

Alfa AF: 0.977 Hom.: 9091

Bravo AF: 0.973

Asia WGS AF: 0.912 AC: 3168 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.4
DANN	Benign	0.33
PhyloP100		0.26
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: rs291465; hg19: chr2-191182961;