15-78171144-G-A

Position:

• chr15-78171144-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IDH3A	NM_005530.3	c.*2139G>A		3_prime_UTR_variant	11/11	ENST00000299518.7
ACSBG1	NM_015162.5	c.*300C>T		3_prime_UTR_variant	14/14	ENST00000258873.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSBG1	ENST00000258873.9	c.*300C>T		3_prime_UTR_variant	14/14	1	NM_015162.5	P1
IDH3A	ENST00000299518.7	c.*2139G>A		3_prime_UTR_variant	11/11	1	NM_005530.3	P1

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9673 AN: 152164 Hom.: 359 Cov.: 33

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.: 0 AF XY: 0.0772 AC XY: 4274 AN XY: 55350

Gnomad4 AFR exome AF: 0.0896

Gnomad4 AMR exome AF: 0.0406

Gnomad4 ASJ exome AF: 0.0956

Gnomad4 EAS exome AF: 0.0299

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.0468

Gnomad4 NFE exome AF: 0.0497

Gnomad4 OTH exome AF: 0.0540

GnomAD4 genome AF: 0.0635 AC: 9675 AN: 152284 Hom.: 358 Cov.: 33 AF XY: 0.0641 AC XY: 4773 AN XY: 74466

Gnomad4 AFR AF: 0.0911

Gnomad4 AMR AF: 0.0409

Gnomad4 ASJ AF: 0.0884

Gnomad4 EAS AF: 0.0291

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.0316

Gnomad4 NFE AF: 0.0496

Gnomad4 OTH AF: 0.0574

Alfa AF: 0.0552 Hom.: 401

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	11
DANN	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs3825847; hg19: chr15-78463486;