chr12-109180060-T-C

Variant names:

• chr12-109180060-T-C
• rs11065772
• NM_001093.4:c.1791T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001093.4(ACACB):​c.1791T>C​(p.Asp597Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 1,611,896 control chromosomes in the GnomAD database, including 518,850 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 0.74 (42467 hom., cov: 31)
  • Exomes 𝑓: 0.81 (476383 hom.)
• Consequence: ACACB NM_001093.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519
• Publications: 21 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.519 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.1791T>C	p.Asp597Asp	synonymous_variant	Exon 11 of 53	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.1791T>C	p.Asp597Asp	synonymous_variant	Exon 11 of 53	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.1791T>C	p.Asp597Asp	synonymous_variant	Exon 10 of 52	1		ENSP00000367079.3
ACACB	ENST00000377854.9	c.-2212T>C		5_prime_UTR_variant	Exon 10 of 47	5		ENSP00000367085.6
ACACB	ENST00000543080.1	n.*20T>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111884 AN: 151922 Hom.: 42466 Cov.: 31

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.774

GnomAD2 exomes AF: 0.769 AC: 193199 AN: 251134 AF XY: 0.781

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.616

Gnomad ASJ exome AF: 0.904

Gnomad EAS exome AF: 0.726

Gnomad FIN exome AF: 0.829

Gnomad NFE exome AF: 0.832

Gnomad OTH exome AF: 0.804

GnomAD4 exome AF: 0.805 AC: 1175436 AN: 1459856 Hom.: 476383 Cov.: 63 AF XY: 0.806 AC XY: 585309 AN XY: 726104

African (AFR) AF: 0.548 AC: 18308 AN: 33424

American (AMR) AF: 0.619 AC: 27662 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 23590 AN: 26134

East Asian (EAS) AF: 0.713 AC: 28277 AN: 39674

South Asian (SAS) AF: 0.755 AC: 65080 AN: 86186

European-Finnish (FIN) AF: 0.830 AC: 44329 AN: 53414

Middle Eastern (MID) AF: 0.832 AC: 3749 AN: 4506

European-Non Finnish (NFE) AF: 0.824 AC: 916379 AN: 1111574

Other (OTH) AF: 0.798 AC: 48062 AN: 60232

GnomAD4 genome AF: 0.736 AC: 111923 AN: 152040 Hom.: 42467 Cov.: 31 AF XY: 0.737 AC XY: 54798 AN XY: 74334

African (AFR) AF: 0.562 AC: 23287 AN: 41424

American (AMR) AF: 0.672 AC: 10270 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3147 AN: 3470

East Asian (EAS) AF: 0.729 AC: 3759 AN: 5156

South Asian (SAS) AF: 0.746 AC: 3597 AN: 4822

European-Finnish (FIN) AF: 0.835 AC: 8844 AN: 10596

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.828 AC: 56303 AN: 67976

Other (OTH) AF: 0.772 AC: 1628 AN: 2108

Alfa AF: 0.799 Hom.: 166333

Bravo AF: 0.717

Asia WGS AF: 0.732 AC: 2544 AN: 3478

EpiCase AF: 0.842

EpiControl AF: 0.844

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.26
PhyloP100		-0.52
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11065772; hg19: chr12-109617865; COSMIC: COSV58141738; COSMIC: COSV58141738;