12-109205890-A-G

Variant names:

• chr12-109205890-A-G
• rs2268387
• NM_001093.4:c.2914-820A>G

Variant summary

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

The NM_001093.4(ACACB):​c.2914-820A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,044 control chromosomes in the GnomAD database, including 10,650 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 (10650 hom., cov: 31)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 13 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.438 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.2914-820A>G		intron	N/A	NP_001084.3
	ACACB	NM_001412734.1		c.2914-820A>G		intron	N/A	NP_001399663.1
	ACACB	NM_001412735.1		c.2914-820A>G		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.2914-820A>G		intron	N/A	ENSP00000341044.7
	ACACB	ENST00000377848.7	TSL:1	c.2914-820A>G		intron	N/A	ENSP00000367079.3
	ACACB	ENST00000377854.9	TSL:5	c.-1089-820A>G		intron	N/A	ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51545 AN: 151924 Hom.: 10654 Cov.: 31

Gnomad AFR AF: 0.0971

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.339 AC: 51542 AN: 152044 Hom.: 10650 Cov.: 31 AF XY: 0.342 AC XY: 25441 AN XY: 74288

African (AFR) AF: 0.0970 AC: 4027 AN: 41536

American (AMR) AF: 0.446 AC: 6800 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1534 AN: 3472

East Asian (EAS) AF: 0.324 AC: 1668 AN: 5144

South Asian (SAS) AF: 0.358 AC: 1726 AN: 4820

European-Finnish (FIN) AF: 0.432 AC: 4555 AN: 10556

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29752 AN: 67968

Other (OTH) AF: 0.387 AC: 817 AN: 2110

Alfa AF: 0.410 Hom.: 24428

Bravo AF: 0.330

Asia WGS AF: 0.313 AC: 1087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.72
DANN	Benign	0.59
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2268387; hg19: chr12-109643695; COSMIC: COSV108162442;