rs3742023

Variant names:

• chr12-109256177-C-T
• rs3742023
• NM_001093.4:c.6204C>T
• ACACB p.His2068His

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.6204C>T​(p.His2068His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,612,772 control chromosomes in the GnomAD database, including 100,135 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 0.30 (7611 hom., cov: 32)
  • Exomes 𝑓: 0.35 (92524 hom.)
• Consequence: ACACB NM_001093.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 32 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=-0.62).
• BP7: Synonymous conserved (PhyloP=-0.56 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001093.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	NM_001093.4	MANE Select	c.6204C>T	p.His2068His	synonymous	Exon 45 of 53	NP_001084.3	O00763-1
	ACACB	NM_001412734.1		c.6204C>T	p.His2068His	synonymous	Exon 46 of 54	NP_001399663.1	O00763-1
	ACACB	NM_001412735.1		c.6204C>T	p.His2068His	synonymous	Exon 45 of 53	NP_001399664.1	O00763-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	ENST00000338432.12	TSL:1 MANE Select	c.6204C>T	p.His2068His	synonymous	Exon 45 of 53	ENSP00000341044.7	O00763-1
	ACACB	ENST00000377848.7	TSL:1	c.6204C>T	p.His2068His	synonymous	Exon 44 of 52	ENSP00000367079.3	O00763-1
	ACACB	ENST00000377854.9	TSL:5	c.2202C>T	p.His734His	synonymous	Exon 44 of 47	ENSP00000367085.6	F8W8T8

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45496 AN: 151834 Hom.: 7610 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.299

GnomAD2 exomes AF: 0.333 AC: 83594 AN: 250862 AF XY: 0.336

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.356

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.271

Gnomad FIN exome AF: 0.435

Gnomad NFE exome AF: 0.354

Gnomad OTH exome AF: 0.347

GnomAD4 exome AF: 0.352 AC: 514176 AN: 1460820 Hom.: 92524 Cov.: 35 AF XY: 0.351 AC XY: 255224 AN XY: 726790

African (AFR) AF: 0.144 AC: 4807 AN: 33470

American (AMR) AF: 0.350 AC: 15636 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 8383 AN: 26116

East Asian (EAS) AF: 0.328 AC: 13013 AN: 39686

South Asian (SAS) AF: 0.298 AC: 25723 AN: 86220

European-Finnish (FIN) AF: 0.430 AC: 22950 AN: 53336

Middle Eastern (MID) AF: 0.276 AC: 1594 AN: 5768

European-Non Finnish (NFE) AF: 0.362 AC: 401758 AN: 1111170

Other (OTH) AF: 0.337 AC: 20312 AN: 60350

GnomAD4 genome AF: 0.299 AC: 45509 AN: 151952 Hom.: 7611 Cov.: 32 AF XY: 0.305 AC XY: 22616 AN XY: 74258

African (AFR) AF: 0.153 AC: 6338 AN: 41458

American (AMR) AF: 0.326 AC: 4984 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1149 AN: 3468

East Asian (EAS) AF: 0.292 AC: 1504 AN: 5146

South Asian (SAS) AF: 0.296 AC: 1426 AN: 4816

European-Finnish (FIN) AF: 0.448 AC: 4721 AN: 10548

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24472 AN: 67934

Other (OTH) AF: 0.301 AC: 635 AN: 2112

Alfa AF: 0.338 Hom.: 18451

Bravo AF: 0.284

Asia WGS AF: 0.298 AC: 1038 AN: 3478

EpiCase AF: 0.344

EpiControl AF: 0.346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.4
DANN	Benign	0.70
PhyloP100		-0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3742023;

hg19: chr12-109693982;

COSMIC: COSV58133707;

COSMIC: COSV58133707;