rs6107100

Variant names:

• chr20-2664039-C-A
• rs6107100
• NM_006899.5:c.37-34G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-2664039-C-A
• chr20-2664039-C-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_006899.5(IDH3B):​c.37-34G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,612,784 control chromosomes in the GnomAD database, including 13,565 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (3778 hom., cov: 32)
  • Exomes 𝑓: 0.099 (9787 hom.)
• Consequence: IDH3B NM_006899.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0560
• Publications: 10 publications found

Genes affected

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]

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

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 20-2664039-C-A is Benign according to our data. Variant chr20-2664039-C-A is described in ClinVar as Benign. ClinVar VariationId is 1276882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDH3B	NM_006899.5	c.37-34G>T		intron_variant	Intron 1 of 11	ENST00000380843.9	NP_008830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDH3B	ENST00000380843.9	c.37-34G>T		intron_variant	Intron 1 of 11	1	NM_006899.5	ENSP00000370223.4
IDH3B	ENST00000474315.5	c.37-34G>T		intron_variant	Intron 1 of 12	1		ENSP00000482773.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26532 AN: 152064 Hom.: 3780 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0786

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.154

GnomAD2 exomes AF: 0.134 AC: 33343 AN: 249532 AF XY: 0.125

Gnomad AFR exome AF: 0.394

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.0436

Gnomad EAS exome AF: 0.229

Gnomad FIN exome AF: 0.0838

Gnomad NFE exome AF: 0.0786

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.0985 AC: 143879 AN: 1460602 Hom.: 9787 Cov.: 34 AF XY: 0.0978 AC XY: 71095 AN XY: 726722

African (AFR) AF: 0.402 AC: 13469 AN: 33464

American (AMR) AF: 0.193 AC: 8609 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.0446 AC: 1164 AN: 26126

East Asian (EAS) AF: 0.233 AC: 9246 AN: 39690

South Asian (SAS) AF: 0.136 AC: 11731 AN: 86236

European-Finnish (FIN) AF: 0.0856 AC: 4569 AN: 53384

Middle Eastern (MID) AF: 0.0922 AC: 532 AN: 5768

European-Non Finnish (NFE) AF: 0.0787 AC: 87485 AN: 1110966

Other (OTH) AF: 0.117 AC: 7074 AN: 60332

GnomAD4 genome AF: 0.175 AC: 26564 AN: 152182 Hom.: 3778 Cov.: 32 AF XY: 0.173 AC XY: 12860 AN XY: 74398

African (AFR) AF: 0.383 AC: 15874 AN: 41476

American (AMR) AF: 0.140 AC: 2140 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1143 AN: 5170

South Asian (SAS) AF: 0.150 AC: 727 AN: 4832

European-Finnish (FIN) AF: 0.0786 AC: 833 AN: 10604

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0784 AC: 5334 AN: 68008

Other (OTH) AF: 0.154 AC: 325 AN: 2110

Alfa AF: 0.101 Hom.: 396

Bravo AF: 0.191

Asia WGS AF: 0.227 AC: 791 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.3
DANN	Benign	0.66
PhyloP100		0.056
PromoterAI		-0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6107100; hg19: chr20-2644685; COSMIC: COSV66484603; COSMIC: COSV66484603;