15-78169115-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015162.5(ACSBG1):c.*2329T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0683 in 606,398 control chromosomes in the GnomAD database, including 1,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.058 (383 hom., cov: 32)
  • Exomes 𝑓: 0.072 (1562 hom.)
• Consequence: ACSBG1 NM_015162.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.596

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 15-78169115-A-G is Benign according to our data. Variant chr15-78169115-A-G is described in ClinVar as [Benign]. Clinvar id is 1230438.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDH3A	NM_005530.3	c.*110A>G		3_prime_UTR_variant	11/11	ENST00000299518.7
ACSBG1	NM_015162.5	c.*2329T>C		3_prime_UTR_variant	14/14	ENST00000258873.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSBG1	ENST00000258873.9	c.*2329T>C		3_prime_UTR_variant	14/14	1	NM_015162.5	P1
IDH3A	ENST00000299518.7	c.*110A>G		3_prime_UTR_variant	11/11	1	NM_005530.3	P1

Frequencies

GnomAD3 genomes AF: 0.0576 AC: 8759 AN: 152154 Hom.: 383 Cov.: 32

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0288

Gnomad ASJ AF: 0.0590

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0860

Gnomad OTH AF: 0.0458

GnomAD4 exome AF: 0.0719 AC: 32653 AN: 454126 Hom.: 1562 Cov.: 7 AF XY: 0.0710 AC XY: 16994 AN XY: 239420

Gnomad4 AFR exome AF: 0.0149

Gnomad4 AMR exome AF: 0.0190

Gnomad4 ASJ exome AF: 0.0569

Gnomad4 EAS exome AF: 0.000164

Gnomad4 SAS exome AF: 0.0135

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.0853

Gnomad4 OTH exome AF: 0.0656

GnomAD4 genome AF: 0.0575 AC: 8757 AN: 152272 Hom.: 383 Cov.: 32 AF XY: 0.0585 AC XY: 4352 AN XY: 74440

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.0288

Gnomad4 ASJ AF: 0.0590

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.0860

Gnomad4 OTH AF: 0.0454

Alfa AF: 0.0729 Hom.: 665

Bravo AF: 0.0469

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	6.8
Dann	Benign	0.85

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: rs17674205; hg19: chr15-78461457;