rs2268404

Variant names:

• chr12-109179051-C-T
• rs2268404
• NM_001093.4:c.1438-37C>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.1438-37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,590,140 control chromosomes in the GnomAD database, including 98 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 0.0030 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (87 hom.)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 1 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.063 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.1438-37C>T		intron	N/A	NP_001084.3
	ACACB	NM_001412734.1		c.1438-37C>T		intron	N/A	NP_001399663.1
	ACACB	NM_001412735.1		c.1438-37C>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.1438-37C>T		intron	N/A	ENSP00000341044.7
	ACACB	ENST00000377848.7	TSL:1	c.1438-37C>T		intron	N/A	ENSP00000367079.3
	ACACB	ENST00000377854.9	TSL:5	c.-2565-37C>T		intron	N/A	ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.00300 AC: 457 AN: 152180 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0685

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00525

GnomAD2 exomes AF: 0.00571 AC: 1265 AN: 221486 AF XY: 0.00545

Gnomad AFR exome AF: 0.00162

Gnomad AMR exome AF: 0.000159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0712

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000609

Gnomad OTH exome AF: 0.00434

GnomAD4 exome AF: 0.00210 AC: 3015 AN: 1437842 Hom.: 87 Cov.: 29 AF XY: 0.00206 AC XY: 1470 AN XY: 714264

African (AFR) AF: 0.000761 AC: 25 AN: 32872

American (AMR) AF: 0.000143 AC: 6 AN: 41952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25684

East Asian (EAS) AF: 0.0598 AC: 2313 AN: 38684

South Asian (SAS) AF: 0.00218 AC: 182 AN: 83544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51664

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5734

European-Non Finnish (NFE) AF: 0.0000656 AC: 72 AN: 1098062

Other (OTH) AF: 0.00696 AC: 415 AN: 59646

GnomAD4 genome AF: 0.00300 AC: 457 AN: 152298 Hom.: 11 Cov.: 32 AF XY: 0.00314 AC XY: 234 AN XY: 74482

African (AFR) AF: 0.000842 AC: 35 AN: 41564

American (AMR) AF: 0.00163 AC: 25 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0689 AC: 357 AN: 5182

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68016

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.000692 Hom.: 0

Bravo AF: 0.00337

Asia WGS AF: 0.0430 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.3
DANN	Benign	0.82
PhyloP100		0.039
Mutation Taster		=100/0	polymorphism

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: rs2268404; hg19: chr12-109616856; COSMIC: COSV58145609;