rs2268384

Variant names:

• chr12-109251588-C-T
• rs2268384
• NM_001093.4:c.5791-458C>T

Variant summary

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

The NM_001093.4(ACACB):​c.5791-458C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,616 control chromosomes in the GnomAD database, including 11,647 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 0.37 (11647 hom., cov: 32)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 3 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 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.5791-458C>T		intron	N/A	NP_001084.3	O00763-1
	ACACB	NM_001412734.1		c.5791-458C>T		intron	N/A	NP_001399663.1	O00763-1
	ACACB	NM_001412735.1		c.5791-458C>T		intron	N/A	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.5791-458C>T		intron	N/A	ENSP00000341044.7	O00763-1
	ACACB	ENST00000377848.7	TSL:1	c.5791-458C>T		intron	N/A	ENSP00000367079.3	O00763-1
	ACACB	ENST00000377854.9	TSL:5	c.1789-458C>T		intron	N/A	ENSP00000367085.6	F8W8T8

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56278 AN: 151498 Hom.: 11645 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.386

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.371 AC: 56286 AN: 151616 Hom.: 11647 Cov.: 32 AF XY: 0.374 AC XY: 27682 AN XY: 74056

African (AFR) AF: 0.186 AC: 7707 AN: 41458

American (AMR) AF: 0.400 AC: 6117 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1480 AN: 3470

East Asian (EAS) AF: 0.317 AC: 1505 AN: 4748

South Asian (SAS) AF: 0.327 AC: 1574 AN: 4816

European-Finnish (FIN) AF: 0.503 AC: 5315 AN: 10558

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31311 AN: 67976

Other (OTH) AF: 0.388 AC: 817 AN: 2108

Alfa AF: 0.420 Hom.: 4816

Bravo AF: 0.355

Asia WGS AF: 0.315 AC: 1092 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.70
PhyloP100		0.15
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: rs2268384; hg19: chr12-109689393;