12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT-CTCCTTCCTTCCTTCCTTCCTTCCT

Variant names:

• chr12-109188171-CTCCTTCCTTCCTTCCT-C
• rs373209583
• NM_001093.4:c.2144+57_2144+72delTTCCTTCCTTCCTTCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001093.4(ACACB):​c.2144+57_2144+72delTTCCTTCCTTCCTTCC variant causes a intron change involving the alteration of a non-conserved nucleotide. 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. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.070 (756 hom., cov: 0)
  • Exomes 𝑓: 0.0059 (414 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-109188171-CTCCTTCCTTCCTTCCT-C is Benign according to our data. Variant chr12-109188171-CTCCTTCCTTCCTTCCT-C is described in ClinVar as Benign. ClinVar VariationId is 773683.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.2144+57_2144+72delTTCCTTCCTTCCTTCC		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+25delTCCTTCCTTCCTTCCT		intron_variant	Intron 13 of 52	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.2144+10_2144+25delTCCTTCCTTCCTTCCT		intron_variant	Intron 12 of 51	1		ENSP00000367079.3
ACACB	ENST00000377854.9	c.-1859+10_-1859+25delTCCTTCCTTCCTTCCT		intron_variant	Intron 12 of 46	5		ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 7368 AN: 105002 Hom.: 754 Cov.: 0

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0211

Gnomad EAS AF: 0.0184

Gnomad SAS AF: 0.00948

Gnomad FIN AF: 0.00213

Gnomad MID AF: 0.0172

Gnomad NFE AF: 0.00640

Gnomad OTH AF: 0.0616

GnomAD2 exomes AF: 0.00883 AC: 1651 AN: 187034 AF XY: 0.00710

Gnomad AFR exome AF: 0.0903

Gnomad AMR exome AF: 0.00819

Gnomad ASJ exome AF: 0.00314

Gnomad EAS exome AF: 0.00729

Gnomad FIN exome AF: 0.000751

Gnomad NFE exome AF: 0.00156

Gnomad OTH exome AF: 0.00543

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00593 AC: 7415 AN: 1251466 Hom.: 414 AF XY: 0.00563 AC XY: 3477 AN XY: 617626

African (AFR) AF: 0.114 AC: 3178 AN: 27826

American (AMR) AF: 0.0152 AC: 544 AN: 35880

Ashkenazi Jewish (ASJ) AF: 0.00963 AC: 211 AN: 21906

East Asian (EAS) AF: 0.0155 AC: 515 AN: 33162

South Asian (SAS) AF: 0.00405 AC: 289 AN: 71396

European-Finnish (FIN) AF: 0.00166 AC: 75 AN: 45230

Middle Eastern (MID) AF: 0.0158 AC: 70 AN: 4418

European-Non Finnish (NFE) AF: 0.00191 AC: 1839 AN: 961100

Other (OTH) AF: 0.0137 AC: 694 AN: 50548

GnomAD4 genome AF: 0.0703 AC: 7389 AN: 105092 Hom.: 756 Cov.: 0 AF XY: 0.0700 AC XY: 3480 AN XY: 49720

African (AFR) AF: 0.232 AC: 6458 AN: 27866

American (AMR) AF: 0.0369 AC: 372 AN: 10074

Ashkenazi Jewish (ASJ) AF: 0.0211 AC: 57 AN: 2698

East Asian (EAS) AF: 0.0185 AC: 60 AN: 3246

South Asian (SAS) AF: 0.00863 AC: 21 AN: 2432

European-Finnish (FIN) AF: 0.00213 AC: 14 AN: 6574

Middle Eastern (MID) AF: 0.0190 AC: 4 AN: 210

European-Non Finnish (NFE) AF: 0.00638 AC: 319 AN: 50016

Other (OTH) AF: 0.0632 AC: 84 AN: 1330

Alfa AF: 0.00558 Hom.: 759

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

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;