rs4766587

chr12-109247525-G-A

Variant summary

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

The NM_001093.4(ACACB):c.5572-81G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 919,252 control chromosomes in the GnomAD database, including 34,224 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 0.23 (4698 hom., cov: 30)
  • Exomes 𝑓: 0.27 (29526 hom.)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACACB	NM_001093.4	c.5572-81G>A		intron_variant		ENST00000338432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACACB	ENST00000338432.12	c.5572-81G>A		intron_variant		1	NM_001093.4	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 34899 AN: 150760 Hom.: 4701 Cov.: 30

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.266 AC: 204445 AN: 768378 Hom.: 29526 AF XY: 0.267 AC XY: 108493 AN XY: 406982

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.387

Gnomad4 SAS exome AF: 0.284

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.251

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.231 AC: 34889 AN: 150874 Hom.: 4698 Cov.: 30 AF XY: 0.235 AC XY: 17308 AN XY: 73718

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.259

Alfa AF: 0.263 Hom.: 5215

Bravo AF: 0.235

Asia WGS AF: 0.331 AC: 1147 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.35
Dann	Benign	0.69

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: rs4766587; hg19: chr12-109685330; COSMIC: COSV58130562; COSMIC: COSV58130562;