chr12-109266520-C-T

Position:

• chr12-109266520-C-T

Variant summary

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

The NM_001093.4(ACACB):​c.*158C>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 0.805 in 905,104 control chromosomes in the GnomAD database, including 294,443 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 0.82 (51082 hom., cov: 32)
  • Exomes 𝑓: 0.80 (243361 hom.)
• Consequence: ACACB NM_001093.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

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]

ACACB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACACB	NM_001093.4	c.*158C>T		3_prime_UTR_variant	53/53	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.*158C>T		3_prime_UTR_variant	53/53	1	NM_001093.4	ENSP00000341044.7

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124444 AN: 152052 Hom.: 51056 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.817

GnomAD4 exome AF: 0.803 AC: 604528 AN: 752934 Hom.: 243361 Cov.: 10 AF XY: 0.800 AC XY: 298555 AN XY: 373410

Gnomad4 AFR exome AF: 0.828

Gnomad4 AMR exome AF: 0.878

Gnomad4 ASJ exome AF: 0.826

Gnomad4 EAS exome AF: 0.762

Gnomad4 SAS exome AF: 0.675

Gnomad4 FIN exome AF: 0.848

Gnomad4 NFE exome AF: 0.808

Gnomad4 OTH exome AF: 0.799

GnomAD4 genome AF: 0.818 AC: 124520 AN: 152170 Hom.: 51082 Cov.: 32 AF XY: 0.819 AC XY: 60899 AN XY: 74398

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.856

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.814

Alfa AF: 0.814 Hom.: 100507

Bravo AF: 0.822

Asia WGS AF: 0.723 AC: 2514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.53

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: rs2075263; hg19: chr12-109704325;