12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT-CTCCTTCCTTCCTTCCTTCCT

Variant names:

• chr12-109188171-CTCCTTCCTTCCTTCCTTCCT-C
• rs373209583
• NM_001093.4:c.2144+53_2144+72delTTCCTTCCTTCCTTCCTTCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001093.4(ACACB):​c.2144+53_2144+72delTTCCTTCCTTCCTTCCTTCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00379 in 1,357,006 control chromosomes in the GnomAD database, including 62 homozygotes. 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 0.017 (36 hom., cov: 0)
  • Exomes 𝑓: 0.0027 (26 hom.)
• 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-CTCCTTCCTTCCTTCCTTCCT-C is Benign according to our data. Variant chr12-109188171-CTCCTTCCTTCCTTCCTTCCT-C is described in ClinVar as Benign. ClinVar VariationId is 771459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0171 (1796/105134) while in subpopulation AFR AF = 0.0468 (1307/27902). AF 95% confidence interval is 0.0447. There are 36 homozygotes in GnomAd4. There are 886 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 Unknown gene

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+53_2144+72delTTCCTTCCTTCCTTCCTTCC		intron	N/A	NP_001084.3	O00763-1
	ACACB	NM_001412734.1		c.2144+53_2144+72delTTCCTTCCTTCCTTCCTTCC		intron	N/A	NP_001399663.1	O00763-1
	ACACB	NM_001412735.1		c.2144+53_2144+72delTTCCTTCCTTCCTTCCTTCC		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+29delTCCTTCCTTCCTTCCTTCCT		intron	N/A	ENSP00000341044.7	O00763-1
	ACACB	ENST00000377848.7	TSL:1	c.2144+10_2144+29delTCCTTCCTTCCTTCCTTCCT		intron	N/A	ENSP00000367079.3	O00763-1
	ACACB	ENST00000377854.9	TSL:5	c.-1859+10_-1859+29delTCCTTCCTTCCTTCCTTCCT		intron	N/A	ENSP00000367085.6	F8W8T8

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 1792 AN: 105044 Hom.: 36 Cov.: 0

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.00619

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.000741

Gnomad EAS AF: 0.00583

Gnomad SAS AF: 0.00247

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00382

Gnomad OTH AF: 0.0114

GnomAD4 exome AF: 0.00267 AC: 3345 AN: 1251872 Hom.: 26 AF XY: 0.00269 AC XY: 1663 AN XY: 617824

African (AFR) AF: 0.0264 AC: 734 AN: 27840

American (AMR) AF: 0.00295 AC: 106 AN: 35890

Ashkenazi Jewish (ASJ) AF: 0.000228 AC: 5 AN: 21918

East Asian (EAS) AF: 0.00639 AC: 212 AN: 33174

South Asian (SAS) AF: 0.000630 AC: 45 AN: 71430

European-Finnish (FIN) AF: 0.0128 AC: 579 AN: 45270

Middle Eastern (MID) AF: 0.00181 AC: 8 AN: 4420

European-Non Finnish (NFE) AF: 0.00150 AC: 1442 AN: 961358

Other (OTH) AF: 0.00423 AC: 214 AN: 50572

GnomAD4 genome AF: 0.0171 AC: 1796 AN: 105134 Hom.: 36 Cov.: 0 AF XY: 0.0178 AC XY: 886 AN XY: 49734

African (AFR) AF: 0.0468 AC: 1307 AN: 27902

American (AMR) AF: 0.0126 AC: 127 AN: 10078

Ashkenazi Jewish (ASJ) AF: 0.000741 AC: 2 AN: 2698

East Asian (EAS) AF: 0.00585 AC: 19 AN: 3246

South Asian (SAS) AF: 0.00247 AC: 6 AN: 2432

European-Finnish (FIN) AF: 0.0190 AC: 125 AN: 6576

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

European-Non Finnish (NFE) AF: 0.00382 AC: 191 AN: 50016

Other (OTH) AF: 0.0113 AC: 15 AN: 1330

Alfa AF: 0.00 Hom.: 759

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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;