Genetic Variant LOC124903534:n.1169A>G (chr15-78146676-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The XR_007064725.1(LOC124903534):n.1169A>G 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 0.55 in 152,056 control chromosomes in the GnomAD database, including 24,002 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 0.55 ( 24001 hom., cov: 32)

Exomes 𝑓: 0.40 ( 1 hom. )

Consequence

LOC124903534
XR_007064725.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.758

Publications

4 publications found

Variant links:

Genes affected

LOC124903534 (HGNC:):

LOC124903534 links:

IDH3A (HGNC:5384): (isocitrate dehydrogenase (NAD(+)) 3 catalytic subunit alpha) 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 alpha subunit of one isozyme of NAD(+)-dependent isocitrate dehydrogenase. [provided by RefSeq, Jul 2008]

IDH3A Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AR Classification: STRONG Submitted by: G2P
retinitis pigmentosa 90
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

IDH3A links:

Genome browser will be placed here

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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903534	XR_007064725.1 link	n.1169A>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDH3A	ENST00000558605.1 link	n.409+86T>C		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.550

AC:

83481

AN:

151896

Hom.:

23983

Cov.:

show subpopulations

Gnomad AFR

AF:

0.707

Gnomad AMI

AF:

0.564

Gnomad AMR

AF:

0.451

Gnomad ASJ

AF:

0.537

Gnomad EAS

AF:

0.297

Gnomad SAS

AF:

0.585

Gnomad FIN

AF:

0.497

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.521

GnomAD4 exome

AF:

0.405

AC:

AN:

Hom.:

AF XY:

0.433

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.406

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.550

AC:

83543

AN:

152014

Hom.:

24001

Cov.:

AF XY:

0.546

AC XY:

40556

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.707

AC:

29286

AN:

41448

American (AMR)

AF:

0.450

AC:

6878

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.537

AC:

1864

AN:

3470

East Asian (EAS)

AF:

0.298

AC:

1539

AN:

5172

South Asian (SAS)

AF:

0.586

AC:

2821

AN:

4818

European-Finnish (FIN)

AF:

0.497

AC:

5245

AN:

10552

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.502

AC:

34115

AN:

67952

Other (OTH)

AF:

0.519

AC:

1098

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1839

3678

5516

7355

9194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.525

Hom.:

3795

Bravo

AF:

0.551

Asia WGS

AF:

0.469

AC:

1631

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.40

(source)

DANN

Benign

0.65

PhyloP100

-0.76

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over