Genetic Variant IDH1-AS1:n.318G>T (chr2-208255534-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000448588.2(IDH1-AS1):n.318G>T 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 0.169 in 152,152 control chromosomes in the GnomAD database, including 2,817 homozygotes. 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: 𝑓 0.17 ( 2817 hom., cov: 33)

Exomes 𝑓: 0.14 ( 0 hom. )

Consequence

IDH1-AS1
ENST00000448588.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850

Publications

23 publications found

Variant links:

Genes affected

IDH1-AS1 (HGNC:40292): (IDH1 antisense RNA 1)

IDH1-AS1 links:

IDH1 (HGNC:5382): (isocitrate dehydrogenase (NADP(+)) 1) 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. Each NADP(+)-dependent isozyme is a homodimer. The protein encoded by this gene is the NADP(+)-dependent isocitrate dehydrogenase found in the cytoplasm and peroxisomes. It contains the PTS-1 peroxisomal targeting signal sequence. The presence of this enzyme in peroxisomes suggests roles in the regeneration of NADPH for intraperoxisomal reductions, such as the conversion of 2, 4-dienoyl-CoAs to 3-enoyl-CoAs, as well as in peroxisomal reactions that consume 2-oxoglutarate, namely the alpha-hydroxylation of phytanic acid. The cytoplasmic enzyme serves a significant role in cytoplasmic NADPH production. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]

IDH1 Gene-Disease associations (from GenCC):

Maffucci syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

IDH1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDH1-AS1	NR_046452.1 link	n.199+103G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
IDH1-AS1	ENST00000448588.2 link	n.318G>T	non_coding_transcript_exon_variant	Exon 1 of 2	3
IDH1-AS1	ENST00000832349.1 link	n.304G>T	non_coding_transcript_exon_variant	Exon 1 of 1
IDH1	ENST00000417583.5 link	c.-217C>A	5_prime_UTR_variant	Exon 1 of 5	4	ENSP00000409045.1

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25725

AN:

151984

Hom.:

2813

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0579

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.486

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.198

GnomAD4 exome

AF:

0.140

AC:

AN:

Hom.:

Cov.:

AF XY:

0.143

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.136

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.554

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.169

AC:

25737

AN:

152102

Hom.:

2817

Cov.:

AF XY:

0.171

AC XY:

12743

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0579

AC:

2406

AN:

41522

American (AMR)

AF:

0.186

AC:

2840

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

792

AN:

3468

East Asian (EAS)

AF:

0.487

AC:

2502

AN:

5134

South Asian (SAS)

AF:

0.233

AC:

1124

AN:

4822

European-Finnish (FIN)

AF:

0.165

AC:

1747

AN:

10604

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.200

AC:

13588

AN:

67930

Other (OTH)

AF:

0.197

AC:

417

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1031

2062

3093

4124

5155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.188

Hom.:

3813

Bravo

AF:

0.170

Asia WGS

AF:

0.321

AC:

1116

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.3

(source)

DANN

Benign

0.80

PhyloP100

0.085

PromoterAI

0.038

Neutral

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over