12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT

Variant names:

• chr12-109188171-CTCCT-C
• rs373209583
• NM_001093.4:c.2144+69_2144+72delTTCC

Variant summary

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

The NM_001093.4(ACACB):​c.2144+69_2144+72delTTCC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (3928 hom., cov: 0)
  • Exomes 𝑓: 0.085 (11924 hom.)
  • Failed GnomAD Quality Control
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.2144+69_2144+72delTTCC		intron_variant	Intron 13 of 52	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12	c.2144+10_2144+13delTCCT		intron_variant	Intron 13 of 52	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.2144+10_2144+13delTCCT		intron_variant	Intron 12 of 51	1		ENSP00000367079.3
ACACB	ENST00000377854.9	c.-1859+10_-1859+13delTCCT		intron_variant	Intron 12 of 46	5		ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.262 AC: 27375 AN: 104640 Hom.: 3926 Cov.: 0

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.241

GnomAD2 exomes AF: 0.0617 AC: 11539 AN: 187034 AF XY: 0.0548

Gnomad AFR exome AF: 0.0574

Gnomad AMR exome AF: 0.0654

Gnomad ASJ exome AF: 0.0419

Gnomad EAS exome AF: 0.0682

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.0603

Gnomad OTH exome AF: 0.0765

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0846 AC: 105663 AN: 1249304 Hom.: 11924 AF XY: 0.0901 AC XY: 55521 AN XY: 616502

African (AFR) AF: 0.0724 AC: 2015 AN: 27820

American (AMR) AF: 0.106 AC: 3798 AN: 35812

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 3320 AN: 21838

East Asian (EAS) AF: 0.171 AC: 5644 AN: 33032

South Asian (SAS) AF: 0.125 AC: 8882 AN: 71256

European-Finnish (FIN) AF: 0.225 AC: 10124 AN: 45054

Middle Eastern (MID) AF: 0.107 AC: 474 AN: 4410

European-Non Finnish (NFE) AF: 0.0684 AC: 65644 AN: 959638

Other (OTH) AF: 0.114 AC: 5762 AN: 50444

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.261 AC: 27377 AN: 104730 Hom.: 3928 Cov.: 0 AF XY: 0.255 AC XY: 12640 AN XY: 49530

African (AFR) AF: 0.181 AC: 5042 AN: 27800

American (AMR) AF: 0.268 AC: 2689 AN: 10024

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 756 AN: 2694

East Asian (EAS) AF: 0.219 AC: 710 AN: 3242

South Asian (SAS) AF: 0.218 AC: 528 AN: 2424

European-Finnish (FIN) AF: 0.275 AC: 1798 AN: 6548

Middle Eastern (MID) AF: 0.248 AC: 52 AN: 210

European-Non Finnish (NFE) AF: 0.309 AC: 15387 AN: 49816

Other (OTH) AF: 0.243 AC: 323 AN: 1328

Alfa AF: 0.165 Hom.: 759

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs373209583; hg19: chr12-109625976; COSMIC: COSV58134893; COSMIC: COSV58134893;