chr12-109197441-C-T

Variant names:

• chr12-109197441-C-T
• rs2268391
• NM_001093.4:c.2627+288C>T

Variant summary

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

The ENST00000338432.12(ACACB):​c.2627+288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,920 control chromosomes in the GnomAD database, including 16,791 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 0.45 (16791 hom., cov: 31)
• Consequence: ACACB ENST00000338432.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000338432.12. 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.2627+288C>T		intron	N/A	NP_001084.3
	ACACB	NM_001412734.1		c.2627+288C>T		intron	N/A	NP_001399663.1
	ACACB	NM_001412735.1		c.2627+288C>T		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.2627+288C>T		intron	N/A	ENSP00000341044.7
	ACACB	ENST00000377848.7	TSL:1	c.2627+288C>T		intron	N/A	ENSP00000367079.3
	ACACB	ENST00000377854.9	TSL:5	c.-1376+288C>T		intron	N/A	ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68470 AN: 151802 Hom.: 16796 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.451 AC: 68472 AN: 151920 Hom.: 16791 Cov.: 31 AF XY: 0.450 AC XY: 33423 AN XY: 74230

African (AFR) AF: 0.255 AC: 10581 AN: 41448

American (AMR) AF: 0.527 AC: 8030 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2006 AN: 3464

East Asian (EAS) AF: 0.264 AC: 1362 AN: 5164

South Asian (SAS) AF: 0.435 AC: 2094 AN: 4814

European-Finnish (FIN) AF: 0.524 AC: 5531 AN: 10556

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36974 AN: 67922

Other (OTH) AF: 0.506 AC: 1064 AN: 2102

Alfa AF: 0.523 Hom.: 10724

Bravo AF: 0.444

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.59
DANN	Benign	0.47
PhyloP100		-1.2
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: rs2268391; hg19: chr12-109635246;