rs11065772

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-109180060-T-C
• chr12-109180060-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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	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

GnomAD3 exomes AF: 0.769 AC: 193199 AN: 251134 Hom.: 75771 AF XY: 0.781 AC XY: 105988 AN XY: 135744

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 SAS exome AF: 0.755

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

Gnomad4 AFR exome AF: 0.548

Gnomad4 AMR exome AF: 0.619

Gnomad4 ASJ exome AF: 0.903

Gnomad4 EAS exome AF: 0.713

Gnomad4 SAS exome AF: 0.755

Gnomad4 FIN exome AF: 0.830

Gnomad4 NFE exome AF: 0.824

Gnomad4 OTH exome AF: 0.798

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

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.907

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.772

Alfa AF: 0.820 Hom.: 112175

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11065772; hg19: chr12-109617865; COSMIC: COSV58141738; COSMIC: COSV58141738;