12-109113703-G-A

Variant names:

• chr12-109113703-G-A
• rs34260
• NM_001412734.1:c.-10+288G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001412734.1(ACACB):​c.-10+288G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,140 control chromosomes in the GnomAD database, including 23,633 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 0.54 (23633 hom., cov: 33)
• Consequence: ACACB NM_001412734.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.44
• Publications: 9 publications found

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]

UNG Gene-Disease associations (from GenCC):

• hyper-IgM syndrome type 5

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ENSG00000256139 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001412734.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	NM_001412734.1		c.-10+288G>A		intron	N/A	NP_001399663.1
	ACACB	NM_001412737.1		c.26+288G>A		intron	N/A	NP_001399666.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNG	ENST00000699563.1		c.774+10092G>A		intron	N/A	ENSP00000514437.1
	ENSG00000256139	ENST00000541704.2	TSL:5	n.576+288G>A		intron	N/A
	ENSG00000256139	ENST00000755021.1		n.485+288G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81527 AN: 152022 Hom.: 23588 Cov.: 33

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.507

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.537 AC: 81625 AN: 152140 Hom.: 23633 Cov.: 33 AF XY: 0.537 AC XY: 39954 AN XY: 74396

African (AFR) AF: 0.761 AC: 31605 AN: 41516

American (AMR) AF: 0.445 AC: 6798 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1609 AN: 3470

East Asian (EAS) AF: 0.707 AC: 3668 AN: 5186

South Asian (SAS) AF: 0.499 AC: 2407 AN: 4820

European-Finnish (FIN) AF: 0.495 AC: 5237 AN: 10586

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28812 AN: 67964

Other (OTH) AF: 0.509 AC: 1076 AN: 2112

Alfa AF: 0.497 Hom.: 7575

Bravo AF: 0.539

Asia WGS AF: 0.609 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.52
PhyloP100		-3.4

Splicing

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

Other links and lift over

dbSNP: rs34260; hg19: chr12-109551508;