12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT-CTCCTTCCTTCCT

Variant names:

• chr12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCTTCCT-C
• rs373209583
• NM_001093.4:c.2144+45_2144+72delTTCCTTCCTTCCTTCCTTCCTTCCTTCC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001093.4(ACACB):​c.2144+45_2144+72delTTCCTTCCTTCCTTCCTTCCTTCCTTCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,357,116 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00044 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.2144+45_2144+72delTTCCTTCCTTCCTTCCTTCCTTCCTTCC		intron	N/A	NP_001084.3	O00763-1
	ACACB	NM_001412734.1		c.2144+45_2144+72delTTCCTTCCTTCCTTCCTTCCTTCCTTCC		intron	N/A	NP_001399663.1	O00763-1
	ACACB	NM_001412735.1		c.2144+45_2144+72delTTCCTTCCTTCCTTCCTTCCTTCCTTCC		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.2144+10_2144+37delTCCTTCCTTCCTTCCTTCCTTCCTTCCT		intron	N/A	ENSP00000341044.7	O00763-1
	ACACB	ENST00000377848.7	TSL:1	c.2144+10_2144+37delTCCTTCCTTCCTTCCTTCCTTCCTTCCT		intron	N/A	ENSP00000367079.3	O00763-1
	ACACB	ENST00000377854.9	TSL:5	c.-1859+10_-1859+37delTCCTTCCTTCCTTCCTTCCTTCCTTCCT		intron	N/A	ENSP00000367085.6	F8W8T8

Frequencies

GnomAD3 genomes AF: 0.000438 AC: 46 AN: 105050 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000298

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000307

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000180

Gnomad OTH AF: 0.00152

GnomAD4 exome AF: 0.000139 AC: 174 AN: 1251976 Hom.: 0 AF XY: 0.000175 AC XY: 108 AN XY: 617868

African (AFR) AF: 0.00136 AC: 38 AN: 27904

American (AMR) AF: 0.000446 AC: 16 AN: 35894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21920

East Asian (EAS) AF: 0.0000301 AC: 1 AN: 33178

South Asian (SAS) AF: 0.000126 AC: 9 AN: 71436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45274

Middle Eastern (MID) AF: 0.00249 AC: 11 AN: 4420

European-Non Finnish (NFE) AF: 0.0000895 AC: 86 AN: 961368

Other (OTH) AF: 0.000257 AC: 13 AN: 50582

GnomAD4 genome AF: 0.000438 AC: 46 AN: 105140 Hom.: 0 Cov.: 0 AF XY: 0.000462 AC XY: 23 AN XY: 49734

African (AFR) AF: 0.00111 AC: 31 AN: 27910

American (AMR) AF: 0.000298 AC: 3 AN: 10078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2698

East Asian (EAS) AF: 0.000308 AC: 1 AN: 3246

South Asian (SAS) AF: 0.00 AC: 0 AN: 2432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 210

European-Non Finnish (NFE) AF: 0.000180 AC: 9 AN: 50016

Other (OTH) AF: 0.00150 AC: 2 AN: 1330

Alfa AF: 0.00 Hom.: 759

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs373209583; hg19: chr12-109625976;