2-190208775-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014362.4(HIBCH):c.1045+105A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0084 in 963,084 control chromosomes in the GnomAD database, including 418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (269 hom., cov: 31)
  • Exomes 𝑓: 0.0040 (149 hom.)
• Consequence: HIBCH NM_014362.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.183

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-190208775-T-G is Benign according to our data. Variant chr2-190208775-T-G is described in ClinVar as [Benign]. Clinvar id is 1296506.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIBCH	NM_014362.4	c.1045+105A>C		intron_variant		ENST00000359678.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIBCH	ENST00000359678.10	c.1045+105A>C		intron_variant		1	NM_014362.4	P1

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4831 AN: 152020 Hom.: 261 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0244

GnomAD3 exomes AF: 0.00865 AC: 1593 AN: 184240 Hom.: 76 AF XY: 0.00648 AC XY: 636 AN XY: 98114

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.00563

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00478

GnomAD4 exome AF: 0.00397 AC: 3220 AN: 810946 Hom.: 149 Cov.: 11 AF XY: 0.00334 AC XY: 1418 AN XY: 424388

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.00672

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000291

Gnomad4 SAS exome AF: 0.000218

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000317

Gnomad4 OTH exome AF: 0.00951

GnomAD4 genome AF: 0.0320 AC: 4870 AN: 152138 Hom.: 269 Cov.: 31 AF XY: 0.0317 AC XY: 2359 AN XY: 74416

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0135

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0180 Hom.: 17

Bravo AF: 0.0369

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.7
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6723335; hg19: chr2-191073501;