Genetic Variant NM_015162.5:c.*300C>T (chr15-78171144-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015162.5(ACSBG1):c.*300C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 257,354 control chromosomes in the GnomAD database, including 752 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 0.064 ( 358 hom., cov: 33)

Exomes 𝑓: 0.068 ( 394 hom. )

Consequence

ACSBG1
NM_015162.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.520

Publications

10 publications found

Variant links:

Genes affected

ACSBG1 (HGNC:29567): (acyl-CoA synthetase bubblegum family member 1) The protein encoded by this gene possesses long-chain acyl-CoA synthetase activity. It is thought to play a central role in brain very long-chain fatty acids metabolism and myelinogenesis. [provided by RefSeq, Jul 2008]

ACSBG1 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=-0.62).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSBG1	NM_015162.5 link	c.*300C>T		3_prime_UTR_variant	Exon 14 of 14	ENST00000258873.9	NP_055977.3
IDH3A	NM_005530.3 link	c.*2139G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000299518.7	NP_005521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSBG1	ENST00000258873.9 link	c.*300C>T		3_prime_UTR_variant	Exon 14 of 14	1	NM_015162.5	ENSP00000258873.4
IDH3A	ENST00000299518.7 link	c.*2139G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_005530.3	ENSP00000299518.2

Frequencies

GnomAD3 genomes

AF:

0.0636

AC:

9673

AN:

152164

Hom.:

359

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0912

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0409

Gnomad ASJ

AF:

0.0884

Gnomad EAS

AF:

0.0288

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.0316

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.0496

Gnomad OTH

AF:

0.0580

GnomAD4 exome

AF:

0.0680

AC:

7147

AN:

105070

Hom.:

394

Cov.:

AF XY:

0.0772

AC XY:

4274

AN XY:

55350

show subpopulations

African (AFR)

AF:

0.0896

AC:

308

AN:

3436

American (AMR)

AF:

0.0406

AC:

193

AN:

4758

Ashkenazi Jewish (ASJ)

AF:

0.0956

AC:

266

AN:

2782

East Asian (EAS)

AF:

0.0299

AC:

168

AN:

5618

South Asian (SAS)

AF:

0.183

AC:

2472

AN:

13490

European-Finnish (FIN)

AF:

0.0468

AC:

234

AN:

4998

Middle Eastern (MID)

AF:

0.0514

AC:

AN:

428

European-Non Finnish (NFE)

AF:

0.0497

AC:

3174

AN:

63816

Other (OTH)

AF:

0.0540

AC:

310

AN:

5744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

308

617

925

1234

1542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.0635

AC:

9675

AN:

152284

Hom.:

358

Cov.:

AF XY:

0.0641

AC XY:

4773

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0911

AC:

3784

AN:

41556

American (AMR)

AF:

0.0409

AC:

625

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0884

AC:

307

AN:

3472

East Asian (EAS)

AF:

0.0291

AC:

151

AN:

5190

South Asian (SAS)

AF:

0.190

AC:

915

AN:

4828

European-Finnish (FIN)

AF:

0.0316

AC:

335

AN:

10596

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0496

AC:

3377

AN:

68030

Other (OTH)

AF:

0.0574

AC:

121

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

485

970

1455

1940

2425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0562

Hom.:

514

Bravo

AF:

0.0608

Asia WGS

AF:

0.124

AC:

431

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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