chr12-109232852-G-C

Variant names:

• chr12-109232852-G-C
• rs3742026
• NM_001093.4:c.4139+46G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001093.4(ACACB):​c.4139+46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,606,722 control chromosomes in the GnomAD database, including 109,431 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 0.34 (9496 hom., cov: 32)
  • Exomes 𝑓: 0.37 (99935 hom.)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.424 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	NM_001093.4	MANE Select	c.4139+46G>C		intron	N/A	NP_001084.3
	ACACB	NM_001412734.1		c.4139+46G>C		intron	N/A	NP_001399663.1
	ACACB	NM_001412735.1		c.4139+46G>C		intron	N/A	NP_001399664.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACB	ENST00000338432.12	TSL:1 MANE Select	c.4139+46G>C		intron	N/A	ENSP00000341044.7
	ACACB	ENST00000377848.7	TSL:1	c.4139+46G>C		intron	N/A	ENSP00000367079.3
	ACACB	ENST00000377854.9	TSL:5	c.137+46G>C		intron	N/A	ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52422 AN: 151884 Hom.: 9506 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.382

GnomAD2 exomes AF: 0.385 AC: 93772 AN: 243756 AF XY: 0.383

Gnomad AFR exome AF: 0.257

Gnomad AMR exome AF: 0.494

Gnomad ASJ exome AF: 0.431

Gnomad EAS exome AF: 0.424

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.373

Gnomad OTH exome AF: 0.383

GnomAD4 exome AF: 0.368 AC: 535131 AN: 1454720 Hom.: 99935 Cov.: 36 AF XY: 0.368 AC XY: 265980 AN XY: 723132

African (AFR) AF: 0.259 AC: 8659 AN: 33396

American (AMR) AF: 0.496 AC: 21978 AN: 44332

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 11023 AN: 25652

East Asian (EAS) AF: 0.356 AC: 14105 AN: 39624

South Asian (SAS) AF: 0.370 AC: 31534 AN: 85264

European-Finnish (FIN) AF: 0.329 AC: 17373 AN: 52772

Middle Eastern (MID) AF: 0.439 AC: 2489 AN: 5672

European-Non Finnish (NFE) AF: 0.366 AC: 405867 AN: 1107920

Other (OTH) AF: 0.368 AC: 22103 AN: 60088

GnomAD4 genome AF: 0.345 AC: 52405 AN: 152002 Hom.: 9496 Cov.: 32 AF XY: 0.342 AC XY: 25448 AN XY: 74302

African (AFR) AF: 0.262 AC: 10874 AN: 41454

American (AMR) AF: 0.433 AC: 6604 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1438 AN: 3468

East Asian (EAS) AF: 0.400 AC: 2064 AN: 5166

South Asian (SAS) AF: 0.365 AC: 1754 AN: 4810

European-Finnish (FIN) AF: 0.324 AC: 3423 AN: 10558

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24928 AN: 67968

Other (OTH) AF: 0.381 AC: 805 AN: 2114

Alfa AF: 0.357 Hom.: 1800

Bravo AF: 0.356

Asia WGS AF: 0.344 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.065
DANN	Benign	0.79
PhyloP100		-1.8
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

Other links and lift over

dbSNP: rs3742026; hg19: chr12-109670657; COSMIC: COSV58149295; COSMIC: COSV58149295;