rs2073192

Variant names:

• chr20-2664350-G-A
• rs2073192
• NR_186432.1:n.77G>A

Variant summary

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

The NR_186432.1(IDH3B-DT):​n.77G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 767,804 control chromosomes in the GnomAD database, including 4,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (656 hom., cov: 33)
  • Exomes 𝑓: 0.097 (3632 hom.)
• Consequence: IDH3B-DT NR_186432.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.478

Genes affected

IDH3B-DT (HGNC:55798): (IDH3B divergent transcript)

IDH3B (HGNC:5385): (isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit beta) 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 beta subunit of one isozyme of NAD(+)-dependent isocitrate dehydrogenase. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 20-2664350-G-A is Benign according to our data. Variant chr20-2664350-G-A is described in ClinVar as [Benign]. Clinvar id is 1261167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDH3B	NM_006899.5	c.-162C>T		upstream_gene_variant		ENST00000380843.9	NP_008830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDH3B	ENST00000380843.9	c.-162C>T		upstream_gene_variant		1	NM_006899.5	ENSP00000370223.4
IDH3B	ENST00000474315.5	c.-162C>T		upstream_gene_variant		1		ENSP00000482773.1

Frequencies

GnomAD3 genomes AF: 0.0780 AC: 11862 AN: 152134 Hom.: 662 Cov.: 33

Gnomad AFR AF: 0.0490

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0999

Gnomad ASJ AF: 0.0346

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0785

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.0827

GnomAD4 exome AF: 0.0971 AC: 59786 AN: 615552 Hom.: 3632 Cov.: 7 AF XY: 0.0980 AC XY: 32066 AN XY: 327326

Gnomad4 AFR exome AF: 0.0493

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.0403

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.0837

Gnomad4 NFE exome AF: 0.0803

Gnomad4 OTH exome AF: 0.0959

GnomAD4 genome AF: 0.0779 AC: 11862 AN: 152252 Hom.: 656 Cov.: 33 AF XY: 0.0792 AC XY: 5897 AN XY: 74440

Gnomad4 AFR AF: 0.0490

Gnomad4 AMR AF: 0.0996

Gnomad4 ASJ AF: 0.0346

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0785

Gnomad4 NFE AF: 0.0780

Gnomad4 OTH AF: 0.0837

Alfa AF: 0.0830 Hom.: 104

Bravo AF: 0.0815

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.3
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2073192; hg19: chr20-2644996;