NM_001093.4:c.-10+2501A>G

Variant names:

• chr12-109119205-A-G
• rs246084
• NM_001093.4:c.-10+2501A>G

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+2501A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,980 control chromosomes in the GnomAD database, including 24,927 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 0.55 (24927 hom., cov: 32)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 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+2501A>G		intron	N/A	NP_001084.3	O00763-1
	ACACB	NM_001412734.1		c.-10+5790A>G		intron	N/A	NP_001399663.1	O00763-1
	ACACB	NM_001412737.1		c.26+5790A>G		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+2501A>G		intron	N/A	ENSP00000341044.7	O00763-1
	UNG	ENST00000699563.1		c.775-6740A>G		intron	N/A	ENSP00000514437.1	A0A8V8TNE1
	ENSG00000256139	ENST00000541704.2	TSL:5	n.576+5790A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84211 AN: 151862 Hom.: 24883 Cov.: 32

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.555 AC: 84310 AN: 151980 Hom.: 24927 Cov.: 32 AF XY: 0.558 AC XY: 41428 AN XY: 74246

African (AFR) AF: 0.747 AC: 30994 AN: 41484

American (AMR) AF: 0.609 AC: 9305 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1609 AN: 3468

East Asian (EAS) AF: 0.724 AC: 3725 AN: 5148

South Asian (SAS) AF: 0.505 AC: 2430 AN: 4812

European-Finnish (FIN) AF: 0.509 AC: 5367 AN: 10548

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29337 AN: 67936

Other (OTH) AF: 0.537 AC: 1130 AN: 2104

Alfa AF: 0.534 Hom.: 3289

Bravo AF: 0.569

Asia WGS AF: 0.629 AC: 2186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.49
PhyloP100		-0.45
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: rs246084; hg19: chr12-109557010;