Variant 2-190208775-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.183

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 linkuse as main transcript	c.1045+105A>C		intron_variant		ENST00000359678.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIBCH	ENST00000359678.10 linkuse as main transcript	c.1045+105A>C		intron_variant		1	NM_014362.4	P1	Q6NVY1-1

Frequencies

GnomAD3 genomes

AF:

0.0318

AC:

4831

AN:

152020

Hom.:

261

Cov.:

show subpopulations

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.:

AF XY:

0.00648

AC XY:

636

AN XY:

98114

show subpopulations

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.:

AF XY:

0.00334

AC XY:

1418

AN XY:

424388

show subpopulations

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.:

AF XY:

0.0317

AC XY:

2359

AN XY:

74416

show subpopulations

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.:

Bravo

AF:

0.0369

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over