rs2075259

Positions:

• chr12-109254186-A-G
• chr12-109254186-A-T

Variant summary

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

The NM_001093.4(ACACB):​c.6046-28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 1,611,184 control chromosomes in the GnomAD database, including 517,634 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.77 (45756 hom., cov: 30)
  • Exomes 𝑓: 0.80 (471878 hom.)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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: This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACACB	NM_001093.4	c.6046-28A>G		intron_variant		ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.6046-28A>G		intron_variant		1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.6046-28A>G		intron_variant		1		ENSP00000367079.3
ACACB	ENST00000377854.9	c.2044-28A>G		intron_variant		5		ENSP00000367085.6
ACACB	ENST00000538526.5	n.2044-28A>G		intron_variant		5		ENSP00000443281.1

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117252 AN: 151832 Hom.: 45753 Cov.: 30

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.782

GnomAD3 exomes AF: 0.793 AC: 198749 AN: 250766 Hom.: 79547 AF XY: 0.789 AC XY: 106931 AN XY: 135584

Gnomad AFR exome AF: 0.662

Gnomad AMR exome AF: 0.879

Gnomad ASJ exome AF: 0.822

Gnomad EAS exome AF: 0.699

Gnomad SAS exome AF: 0.672

Gnomad FIN exome AF: 0.860

Gnomad NFE exome AF: 0.816

Gnomad OTH exome AF: 0.808

GnomAD4 exome AF: 0.803 AC: 1171198 AN: 1459234 Hom.: 471878 Cov.: 38 AF XY: 0.799 AC XY: 579886 AN XY: 726080

Gnomad4 AFR exome AF: 0.662

Gnomad4 AMR exome AF: 0.875

Gnomad4 ASJ exome AF: 0.822

Gnomad4 EAS exome AF: 0.698

Gnomad4 SAS exome AF: 0.675

Gnomad4 FIN exome AF: 0.857

Gnomad4 NFE exome AF: 0.815

Gnomad4 OTH exome AF: 0.789

GnomAD4 genome AF: 0.772 AC: 117293 AN: 151950 Hom.: 45756 Cov.: 30 AF XY: 0.773 AC XY: 57436 AN XY: 74292

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.839

Gnomad4 ASJ AF: 0.837

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.781

Alfa AF: 0.810 Hom.: 50144

Bravo AF: 0.768

Asia WGS AF: 0.701 AC: 2438 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.83
BranchPoint Hunter		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2075259; hg19: chr12-109691991;