12-109167925-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001093.4(ACACB):c.816C>T(p.Ala272=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,613,306 control chromosomes in the GnomAD database, including 36,864 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 0.18 (3042 hom., cov: 28)
  • Exomes 𝑓: 0.21 (33822 hom.)
• Consequence: ACACB NM_001093.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89

Genes affected

ACACB (HGNC:85): (acetyl-CoA carboxylase beta) Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. ACC-beta is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine-palmitoyl-CoA transferase I, the rate-limiting step in fatty acid uptake and oxidation by mitochondria. ACC-beta may be involved in the regulation of fatty acid oxidation, rather than fatty acid biosynthesis. [provided by RefSeq, Oct 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-2.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACACB	NM_001093.4	c.816C>T	p.Ala272=	synonymous_variant	4/53	ENST00000338432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACACB	ENST00000338432.12	c.816C>T	p.Ala272=	synonymous_variant	4/53	1	NM_001093.4	P1
ACACB	ENST00000377848.7	c.816C>T	p.Ala272=	synonymous_variant	3/52	1		P1
ACACB	ENST00000544726.2	c.210C>T	p.Ala70=	synonymous_variant	3/5	3
ACACB	ENST00000377854.9	c.-3187C>T		5_prime_UTR_variant	3/47	5

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27191 AN: 151610 Hom.: 3039 Cov.: 28

Gnomad AFR AF: 0.0709

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.183

GnomAD3 exomes AF: 0.233 AC: 58490 AN: 251142 Hom.: 8215 AF XY: 0.233 AC XY: 31571 AN XY: 135746

Gnomad AFR exome AF: 0.0690

Gnomad AMR exome AF: 0.260

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.549

Gnomad SAS exome AF: 0.255

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.216

GnomAD4 exome AF: 0.206 AC: 301470 AN: 1461578 Hom.: 33822 Cov.: 34 AF XY: 0.208 AC XY: 150888 AN XY: 727082

Gnomad4 AFR exome AF: 0.0638

Gnomad4 AMR exome AF: 0.251

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.507

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.209

GnomAD4 genome AF: 0.179 AC: 27204 AN: 151728 Hom.: 3042 Cov.: 28 AF XY: 0.184 AC XY: 13634 AN XY: 74096

Gnomad4 AFR AF: 0.0708

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.186

Alfa AF: 0.181 Hom.: 1287

Bravo AF: 0.175

Asia WGS AF: 0.346 AC: 1205 AN: 3478

EpiCase AF: 0.189

EpiControl AF: 0.191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.32
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4766516; hg19: chr12-109605730; COSMIC: COSV58131765; COSMIC: COSV58131765;