2-208257535-T-C

Variant names:

• chr2-208257535-T-C
• rs7580715
• ENST00000451391.5:c.-272-1946A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000451391.5(IDH1):​c.-272-1946A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 152,306 control chromosomes in the GnomAD database, including 69,599 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 0.95 (69599 hom., cov: 33)
• Consequence: IDH1 ENST00000451391.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• Maffucci syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDH1	ENST00000451391.5	c.-272-1946A>G		intron_variant	Intron 1 of 5	3		ENSP00000396787.1

Frequencies

GnomAD3 genomes AF: 0.955 AC: 145265 AN: 152188 Hom.: 69553 Cov.: 33

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.967

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.954 AC: 145368 AN: 152306 Hom.: 69599 Cov.: 33 AF XY: 0.956 AC XY: 71236 AN XY: 74478

African (AFR) AF: 0.867 AC: 36024 AN: 41548

American (AMR) AF: 0.980 AC: 14997 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 3465 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5170 AN: 5184

South Asian (SAS) AF: 0.996 AC: 4804 AN: 4824

European-Finnish (FIN) AF: 0.998 AC: 10604 AN: 10622

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.986 AC: 67062 AN: 68036

Other (OTH) AF: 0.968 AC: 2044 AN: 2112

Alfa AF: 0.967 Hom.: 9579

Bravo AF: 0.949

Asia WGS AF: 0.985 AC: 3427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.10
DANN	Benign	0.33
PhyloP100		-2.6

Splicing

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

Other links and lift over

dbSNP: rs7580715; hg19: chr2-209122259;