12-109113428-G-C

Variant names:

• chr12-109113428-G-C
• rs34259
• NM_001412734.1:c.-10+13G>C

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+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
• Publications: 12 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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000256139 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	NM_001412734.1		c.-10+13G>C		intron	N/A	NP_001399663.1	O00763-1
	ACACB	NM_001412737.1		c.26+13G>C		intron	N/A	NP_001399666.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNG	ENST00000699563.1		c.774+9817G>C		intron	N/A	ENSP00000514437.1	A0A8V8TNE1
	ENSG00000256139	ENST00000755022.1		n.664G>C		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000256139	ENST00000541704.2	TSL:5	n.576+13G>C		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 3 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.425 AC: 17613 AN: 41488

American (AMR) AF: 0.179 AC: 2744 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3472

East Asian (EAS) AF: 0.105 AC: 544 AN: 5178

South Asian (SAS) AF: 0.220 AC: 1059 AN: 4824

European-Finnish (FIN) AF: 0.223 AC: 2351 AN: 10564

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14555 AN: 68002

Other (OTH) AF: 0.261 AC: 551 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.57
PhyloP100		-0.44

Splicing

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

Other links and lift over

dbSNP: rs34259; hg19: chr12-109551233;