15-78149232-C-G

Position:

• chr15-78149232-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000558605.1(IDH3A):​n.409+2642C>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 683,870 control chromosomes in the GnomAD database, including 1,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (378 hom., cov: 31)
  • Exomes 𝑓: 0.056 (1151 hom.)
• Consequence: IDH3A ENST00000558605.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.597

Genes affected

IDH3A (HGNC:5384): (isocitrate dehydrogenase (NAD(+)) 3 catalytic subunit alpha) Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. NAD(+)-dependent isocitrate dehydrogenases catalyze the allosterically regulated rate-limiting step of the tricarboxylic acid cycle. Each isozyme is a heterotetramer that is composed of two alpha subunits, one beta subunit, and one gamma subunit. The protein encoded by this gene is the alpha subunit of one isozyme of NAD(+)-dependent isocitrate dehydrogenase. [provided by RefSeq, Jul 2008]

LOC124903534 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 15-78149232-C-G is Benign according to our data. Variant chr15-78149232-C-G is described in ClinVar as [Benign]. Clinvar id is 1263132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124903534	XR_007064725.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDH3A	ENST00000558605.1	n.409+2642C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9832 AN: 151872 Hom.: 380 Cov.: 31

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.0290

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.0577

GnomAD4 exome AF: 0.0558 AC: 29675 AN: 531880 Hom.: 1151 AF XY: 0.0592 AC XY: 16021 AN XY: 270738

Gnomad4 AFR exome AF: 0.0913

Gnomad4 AMR exome AF: 0.0340

Gnomad4 ASJ exome AF: 0.0772

Gnomad4 EAS exome AF: 0.0381

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.0397

Gnomad4 NFE exome AF: 0.0478

Gnomad4 OTH exome AF: 0.0565

GnomAD4 genome AF: 0.0647 AC: 9832 AN: 151990 Hom.: 378 Cov.: 31 AF XY: 0.0659 AC XY: 4898 AN XY: 74308

Gnomad4 AFR AF: 0.0912

Gnomad4 AMR AF: 0.0408

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.0417

Gnomad4 NFE AF: 0.0498

Gnomad4 OTH AF: 0.0571

Alfa AF: 0.0563 Hom.: 38

Bravo AF: 0.0610

Asia WGS AF: 0.129 AC: 446 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	17
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs62009333; hg19: chr15-78441574;