Variant rs2289329 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_002225.5(IVD):c.688-31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,595,266 control chromosomes in the GnomAD database, including 146,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.38 ( 12105 hom., cov: 33)

Exomes 𝑓: 0.42 ( 134153 hom. )

Consequence

IVD
NM_002225.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.944

Variant links:

Genes affected

IVD (HGNC:6186): (isovaleryl-CoA dehydrogenase) Isovaleryl-CoA dehydrogenase (IVD) is a mitochondrial matrix enzyme that catalyzes the third step in leucine catabolism. The genetic deficiency of IVD results in an accumulation of isovaleric acid, which is toxic to the central nervous system and leads to isovaleric acidemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2017]

IVD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but rather VUS (scored 4 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 15-40412960-T-C is Benign according to our data. Variant chr15-40412960-T-C is described in ClinVar as [Benign]. Clinvar id is 258591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IVD	NM_002225.5 linkuse as main transcript	c.688-31T>C		intron_variant		ENST00000487418.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IVD	ENST00000487418.8 linkuse as main transcript	c.688-31T>C		intron_variant		1	NM_002225.5	P4

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57097

AN:

151972

Hom.:

12099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.770

Gnomad SAS

AF:

0.625

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.387

GnomAD3 exomes

AF:

0.467

AC:

117090

AN:

250492

Hom.:

29691

AF XY:

0.474

AC XY:

64131

AN XY:

135362

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.557

Gnomad ASJ exome

AF:

0.438

Gnomad EAS exome

AF:

0.776

Gnomad SAS exome

AF:

0.619

Gnomad FIN exome

AF:

0.452

Gnomad NFE exome

AF:

0.394

Gnomad OTH exome

AF:

0.438

GnomAD4 exome

AF:

0.420

AC:

606054

AN:

1443176

Hom.:

134153

Cov.:

AF XY:

0.426

AC XY:

306508

AN XY:

719030

show subpopulations

Gnomad4 AFR exome

AF:

0.199

Gnomad4 AMR exome

AF:

0.546

Gnomad4 ASJ exome

AF:

0.432

Gnomad4 EAS exome

AF:

0.806

Gnomad4 SAS exome

AF:

0.621

Gnomad4 FIN exome

AF:

0.452

Gnomad4 NFE exome

AF:

0.390

Gnomad4 OTH exome

AF:

0.418

GnomAD4 genome

AF:

0.376

AC:

57128

AN:

152090

Hom.:

12105

Cov.:

AF XY:

0.386

AC XY:

28684

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.205

Gnomad4 AMR

AF:

0.459

Gnomad4 ASJ

AF:

0.427

Gnomad4 EAS

AF:

0.770

Gnomad4 SAS

AF:

0.626

Gnomad4 FIN

AF:

0.461

Gnomad4 NFE

AF:

0.395

Gnomad4 OTH

AF:

0.389

Alfa

AF:

0.392

Hom.:

12329

Bravo

AF:

0.368

Asia WGS

AF:

0.602

AC:

2091

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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	Mar 03, 2015	- -

Isovaleryl-CoA dehydrogenase deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.76

BranchPoint Hunter

4.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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