2-208255534-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000451391.5(IDH1):​c.-217C>A variant causes a 5 prime UTR 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
ENST00000451391.5 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850
Variant links:
Genes affected
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-AS1 (HGNC:40292): (IDH1 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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-AS1NR_046452.1 linkn.199+103G>T intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IDH1ENST00000417583.5 linkc.-217C>A 5_prime_UTR_variant Exon 1 of 5 4 ENSP00000409045.1 C9JLU6
IDH1ENST00000451391.5 linkc.-217C>A 5_prime_UTR_variant Exon 2 of 6 3 ENSP00000396787.1 C9JJE5
IDH1-AS1ENST00000448588.1 linkn.135G>T non_coding_transcript_exon_variant Exon 1 of 2 3
IDH1-AS1ENST00000440574.2 linkn.218+103G>T intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
AF:
0.169
AC:
25725
AN:
151984
Hom.:
2813
Cov.:
33
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:
7
AN:
50
Hom.:
0
Cov.:
0
AF XY:
0.143
AC XY:
6
AN XY:
42
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.500
Gnomad4 NFE exome
AF:
0.136
GnomAD4 genome
AF:
0.169
AC:
25737
AN:
152102
Hom.:
2817
Cov.:
33
AF XY:
0.171
AC XY:
12743
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.0579
Gnomad4 AMR
AF:
0.186
Gnomad4 ASJ
AF:
0.228
Gnomad4 EAS
AF:
0.487
Gnomad4 SAS
AF:
0.233
Gnomad4 FIN
AF:
0.165
Gnomad4 NFE
AF:
0.200
Gnomad4 OTH
AF:
0.197
Alfa
AF:
0.192
Hom.:
3092
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
DANN
Benign
0.80

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12478635; hg19: chr2-209120258; API