rs2562796

Positions:

• chr2-190248283-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIBCH	NM_014362.4	c.750+1357A>C		intron_variant		ENST00000359678.10	NP_055177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIBCH	ENST00000359678.10	c.750+1357A>C		intron_variant		1	NM_014362.4	ENSP00000352706	P1

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

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.310

Alfa AF: 0.261 Hom.: 951

Bravo AF: 0.315

Asia WGS AF: 0.346 AC: 1201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.67

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: rs2562796; hg19: chr2-191113009;