rs2878960

chr12-109139930-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001093.4(ACACB):c.525C>T(p.Ser175=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,613,780 control chromosomes in the GnomAD database, including 319,608 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 0.52 (23075 hom., cov: 32)
  • Exomes 𝑓: 0.63 (296533 hom.)
• Consequence: ACACB NM_001093.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98

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=-0.7).
• BP7: Synonymous conserved (PhyloP=-2.98 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACACB	NM_001093.4	c.525C>T	p.Ser175=	synonymous_variant	2/53	ENST00000338432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACACB	ENST00000338432.12	c.525C>T	p.Ser175=	synonymous_variant	2/53	1	NM_001093.4	P1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79701 AN: 151966 Hom.: 23084 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.564

GnomAD3 exomes AF: 0.553 AC: 138337 AN: 250234 Hom.: 41507 AF XY: 0.567 AC XY: 76824 AN XY: 135396

Gnomad AFR exome AF: 0.296

Gnomad AMR exome AF: 0.375

Gnomad ASJ exome AF: 0.640

Gnomad EAS exome AF: 0.256

Gnomad SAS exome AF: 0.510

Gnomad FIN exome AF: 0.666

Gnomad NFE exome AF: 0.672

Gnomad OTH exome AF: 0.609

GnomAD4 exome AF: 0.628 AC: 917292 AN: 1461696 Hom.: 296533 Cov.: 77 AF XY: 0.627 AC XY: 456239 AN XY: 727156

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.384

Gnomad4 ASJ exome AF: 0.638

Gnomad4 EAS exome AF: 0.228

Gnomad4 SAS exome AF: 0.517

Gnomad4 FIN exome AF: 0.661

Gnomad4 NFE exome AF: 0.669

Gnomad4 OTH exome AF: 0.608

GnomAD4 genome AF: 0.524 AC: 79686 AN: 152084 Hom.: 23075 Cov.: 32 AF XY: 0.520 AC XY: 38691 AN XY: 74352

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.560

Alfa AF: 0.635 Hom.: 60678

Bravo AF: 0.500

Asia WGS AF: 0.372 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	0.076
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs2878960; hg19: chr12-109577735; COSMIC: COSV58135326; COSMIC: COSV58135326;