2-190318235-C-G

Position:

• chr2-190318235-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIBCH	NM_014362.4	c.35+1481G>C		intron_variant		ENST00000359678.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIBCH	ENST00000359678.10	c.35+1481G>C		intron_variant		1	NM_014362.4	P1
HIBCH	ENST00000392332.7	c.35+1481G>C		intron_variant		1
HIBCH	ENST00000409934.1	c.198-7439G>C		intron_variant		3

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

Gnomad4 AFR AF: 0.974

Gnomad4 AMR AF: 0.985

Gnomad4 ASJ AF: 0.980

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.934

Gnomad4 FIN AF: 0.985

Gnomad4 NFE AF: 0.979

Gnomad4 OTH AF: 0.965

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.4
DANN	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs291465; hg19: chr2-191182961;