12-109191652-C-T

Variant names:

• chr12-109191652-C-T
• rs7135947
• NM_001093.4:c.2184C>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.2184C>T​(p.Gly728Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,613,776 control chromosomes in the GnomAD database, including 213,475 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 0.45 (16637 hom., cov: 32)
  • Exomes 𝑓: 0.51 (196838 hom.)
• Consequence: ACACB NM_001093.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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=-0.71).
• BP7: Synonymous conserved (PhyloP=-2.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.2184C>T	p.Gly728Gly	synonymous_variant	Exon 14 of 53	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.2184C>T	p.Gly728Gly	synonymous_variant	Exon 14 of 53	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.2184C>T	p.Gly728Gly	synonymous_variant	Exon 13 of 52	1		ENSP00000367079.3
ACACB	ENST00000377854	c.-1819C>T		5_prime_UTR_variant	Exon 13 of 47	5		ENSP00000367085.6
ACACB	ENST00000544651.1	n.175C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68266 AN: 151904 Hom.: 16640 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.503

GnomAD3 exomes AF: 0.493 AC: 123965 AN: 251404 Hom.: 31947 AF XY: 0.498 AC XY: 67671 AN XY: 135874

Gnomad AFR exome AF: 0.256

Gnomad AMR exome AF: 0.545

Gnomad ASJ exome AF: 0.573

Gnomad EAS exome AF: 0.272

Gnomad SAS exome AF: 0.447

Gnomad FIN exome AF: 0.521

Gnomad NFE exome AF: 0.545

Gnomad OTH exome AF: 0.535

GnomAD4 exome AF: 0.515 AC: 752291 AN: 1461754 Hom.: 196838 Cov.: 54 AF XY: 0.515 AC XY: 374210 AN XY: 727180

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.567

Gnomad4 EAS exome AF: 0.256

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.502

GnomAD4 genome AF: 0.449 AC: 68275 AN: 152022 Hom.: 16637 Cov.: 32 AF XY: 0.449 AC XY: 33328 AN XY: 74302

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.500

Alfa AF: 0.523 Hom.: 41922

Bravo AF: 0.442

Asia WGS AF: 0.370 AC: 1284 AN: 3476

EpiCase AF: 0.562

EpiControl AF: 0.559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.15
DANN	Benign	0.72

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: rs7135947; hg19: chr12-109629457; COSMIC: COSV58130613;