12-109113428-G-C

Position:

• chr12-109113428-G-C

Variant summary

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

The NM_001412734.1(ACACB):​c.-10+13G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,146 control chromosomes in the GnomAD database, including 6,108 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 0.26 (6107 hom., cov: 33)
  • Exomes 𝑓: 0.38 (1 hom.)
• Consequence: ACACB NM_001412734.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

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]

UNG (HGNC:12572): (uracil DNA glycosylase) This gene encodes one of several uracil-DNA glycosylases. One important function of uracil-DNA glycosylases is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosylic bond and initiating the base-excision repair (BER) pathway. Uracil bases occur from cytosine deamination or misincorporation of dUMP residues. Alternative promoter usage and splicing of this gene leads to two different isoforms: the mitochondrial UNG1 and the nuclear UNG2. The UNG2 term was used as a previous symbol for the CCNO gene (GeneID 10309), which has been confused with this gene, in the literature and some databases. [provided by RefSeq, Nov 2010]

ENSG00000256139 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACACB	NM_001412734.1	c.-10+13G>C		intron_variant			NP_001399663.1
ACACB	NM_001412737.1	c.26+13G>C		intron_variant			NP_001399666.1
ACACB	XM_011538263.4	c.-10+13G>C		intron_variant			XP_011536565.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNG	ENST00000699563.1	c.774+9817G>C		intron_variant				ENSP00000514437.1
ENSG00000256139	ENST00000541704.2	n.576+13G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40206 AN: 152020 Hom.: 6104 Cov.: 33

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.265 AC: 40242 AN: 152138 Hom.: 6107 Cov.: 33 AF XY: 0.261 AC XY: 19431 AN XY: 74376

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.261

Alfa AF: 0.145 Hom.: 283

Bravo AF: 0.264

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34259; hg19: chr12-109551233;