chr12-109247740-A-G

Variant names:

• chr12-109247740-A-G
• rs2284689
• NM_001093.4:c.5669+37A>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.5669+37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 1,531,376 control chromosomes in the GnomAD database, including 495,798 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 0.77 (46151 hom., cov: 32)
  • Exomes 𝑓: 0.81 (449647 hom.)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 14 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]

ACACB Gene-Disease associations (from GenCC):

• isolated cleft palate

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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 (AMR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.5669+37A>G		intron_variant	Intron 40 of 52	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.5669+37A>G		intron_variant	Intron 40 of 52	1	NM_001093.4	ENSP00000341044.7

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117775 AN: 151960 Hom.: 46133 Cov.: 32

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.782

GnomAD2 exomes AF: 0.798 AC: 195944 AN: 245392 AF XY: 0.794

Gnomad AFR exome AF: 0.663

Gnomad AMR exome AF: 0.879

Gnomad ASJ exome AF: 0.823

Gnomad EAS exome AF: 0.763

Gnomad FIN exome AF: 0.860

Gnomad NFE exome AF: 0.817

Gnomad OTH exome AF: 0.811

GnomAD4 exome AF: 0.806 AC: 1111727 AN: 1379298 Hom.: 449647 Cov.: 20 AF XY: 0.802 AC XY: 553670 AN XY: 690370

African (AFR) AF: 0.665 AC: 21036 AN: 31640

American (AMR) AF: 0.875 AC: 38620 AN: 44136

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 21000 AN: 25544

East Asian (EAS) AF: 0.773 AC: 30319 AN: 39234

South Asian (SAS) AF: 0.682 AC: 56960 AN: 83560

European-Finnish (FIN) AF: 0.858 AC: 45345 AN: 52876

Middle Eastern (MID) AF: 0.788 AC: 4125 AN: 5232

European-Non Finnish (NFE) AF: 0.817 AC: 848615 AN: 1039322

Other (OTH) AF: 0.791 AC: 45707 AN: 57754

GnomAD4 genome AF: 0.775 AC: 117842 AN: 152078 Hom.: 46151 Cov.: 32 AF XY: 0.777 AC XY: 57738 AN XY: 74348

African (AFR) AF: 0.668 AC: 27663 AN: 41432

American (AMR) AF: 0.841 AC: 12866 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2908 AN: 3472

East Asian (EAS) AF: 0.755 AC: 3900 AN: 5166

South Asian (SAS) AF: 0.669 AC: 3213 AN: 4802

European-Finnish (FIN) AF: 0.860 AC: 9112 AN: 10598

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55620 AN: 67998

Other (OTH) AF: 0.782 AC: 1649 AN: 2110

Alfa AF: 0.802 Hom.: 36405

Bravo AF: 0.770

Asia WGS AF: 0.722 AC: 2512 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.037
DANN	Benign	0.24
PhyloP100		-1.1
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: rs2284689; hg19: chr12-109685545;