dbSNP rs10518693: IVD:c.234+98C>G (chr15-40407823-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002225.5(IVD):c.234+98C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000078 in 1,282,554 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

IVD
NM_002225.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0380

Publications

40 publications found

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 Gene-Disease associations (from GenCC):

isovaleric acidemia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health, G2P, ClinGen

IVD links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IVD	NM_002225.5 link	c.234+98C>G		intron_variant	Intron 2 of 11	ENST00000487418.8	NP_002216.3	P26440A0A0A0MT83

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IVD	ENST00000487418.8 link	c.234+98C>G		intron_variant	Intron 2 of 11	1	NM_002225.5	ENSP00000418397.3		A0A0A0MT83

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.80e-7

AC:

AN:

1282554

Hom.:

Cov.:

AF XY:

0.00000155

AC XY:

AN XY:

647244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29882

American (AMR)

AF:

0.00

AC:

AN:

44394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24976

East Asian (EAS)

AF:

0.00

AC:

AN:

38776

South Asian (SAS)

AF:

0.00

AC:

AN:

82474

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4266

European-Non Finnish (NFE)

AF:

0.00000105

AC:

AN:

950188

Other (OTH)

AF:

0.00

AC:

AN:

54276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.0

(source)

DANN

Benign

0.63

PhyloP100

0.038

PromoterAI

0.0047

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over