12-109124475-G-T

Variant names:

• chr12-109124475-G-T
• rs2430682
• NM_001093.4:c.-10+7771G>T

Variant summary

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

The NM_001093.4(ACACB):​c.-10+7771G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,032 control chromosomes in the GnomAD database, including 22,709 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 0.53 (22709 hom., cov: 32)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943
• 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

LOC105369974 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001093.4. 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_001093.4	MANE Select	c.-10+7771G>T		intron	N/A	NP_001084.3	O00763-1
	ACACB	NM_001412734.1		c.-10+11060G>T		intron	N/A	NP_001399663.1	O00763-1
	ACACB	NM_001412737.1		c.26+11060G>T		intron	N/A	NP_001399666.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	ENST00000338432.12	TSL:1 MANE Select	c.-10+7771G>T		intron	N/A	ENSP00000341044.7	O00763-1
	UNG	ENST00000699563.1		c.775-1470G>T		intron	N/A	ENSP00000514437.1	A0A8V8TNE1
	ENSG00000256139	ENST00000541704.2	TSL:5	n.577-786G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80279 AN: 151912 Hom.: 22673 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.529 AC: 80369 AN: 152032 Hom.: 22709 Cov.: 32 AF XY: 0.531 AC XY: 39431 AN XY: 74324

African (AFR) AF: 0.734 AC: 30428 AN: 41476

American (AMR) AF: 0.442 AC: 6750 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1610 AN: 3470

East Asian (EAS) AF: 0.701 AC: 3627 AN: 5174

South Asian (SAS) AF: 0.505 AC: 2439 AN: 4828

European-Finnish (FIN) AF: 0.495 AC: 5225 AN: 10552

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28813 AN: 67930

Other (OTH) AF: 0.506 AC: 1067 AN: 2110

Alfa AF: 0.437 Hom.: 7980

Bravo AF: 0.529

Asia WGS AF: 0.606 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.67
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2430682; hg19: chr12-109562280;