rs3791789

chr2-190220095-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIBCH	NM_014362.4	c.892-7020A>G		intron_variant		ENST00000359678.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIBCH	ENST00000359678.10	c.892-7020A>G		intron_variant		1	NM_014362.4	P1

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

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.320

Alfa AF: 0.267 Hom.: 1026

Bravo AF: 0.329

Asia WGS AF: 0.352 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	6.8
Dann	Benign	0.66

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: rs3791789; hg19: chr2-191084821;