12-109205840-G-A

Variant names:

• chr12-109205840-G-A
• rs2268388
• NM_001093.4:c.2914-870G>A

Variant summary

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

The NM_001093.4(ACACB):​c.2914-870G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,006 control chromosomes in the GnomAD database, including 1,593 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 0.14 (1593 hom., cov: 31)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• Publications: 45 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 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.2914-870G>A		intron	N/A	NP_001084.3
	ACACB	NM_001412734.1		c.2914-870G>A		intron	N/A	NP_001399663.1
	ACACB	NM_001412735.1		c.2914-870G>A		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.2914-870G>A		intron	N/A	ENSP00000341044.7
	ACACB	ENST00000377848.7	TSL:1	c.2914-870G>A		intron	N/A	ENSP00000367079.3
	ACACB	ENST00000377854.9	TSL:5	c.-1089-870G>A		intron	N/A	ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21381 AN: 151888 Hom.: 1587 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.141 AC: 21407 AN: 152006 Hom.: 1593 Cov.: 31 AF XY: 0.140 AC XY: 10370 AN XY: 74312

African (AFR) AF: 0.131 AC: 5445 AN: 41462

American (AMR) AF: 0.122 AC: 1866 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1154 AN: 5138

South Asian (SAS) AF: 0.176 AC: 851 AN: 4824

European-Finnish (FIN) AF: 0.134 AC: 1417 AN: 10574

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9910 AN: 67978

Other (OTH) AF: 0.144 AC: 304 AN: 2108

Alfa AF: 0.146 Hom.: 1914

Bravo AF: 0.141

Asia WGS AF: 0.213 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.44
PhyloP100		-0.68
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: rs2268388; hg19: chr12-109643645;