12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT-CTCCTTCCTTCCTTCCTTCCTTCCTTCCT

Variant names:

• chr12-109188171-CTCCTTCCTTCCT-C
• rs373209583
• NM_001093.4:c.2144+61_2144+72delTTCCTTCCTTCC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001093.4(ACACB):​c.2144+61_2144+72delTTCCTTCCTTCC 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 0.10 (684 hom., cov: 0)
  • Exomes 𝑓: 0.028 (1633 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 12-109188171-CTCCTTCCTTCCT-C is Benign according to our data. Variant chr12-109188171-CTCCTTCCTTCCT-C is described in ClinVar as Benign. ClinVar VariationId is 768580.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.2144+61_2144+72delTTCCTTCCTTCC		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+21delTCCTTCCTTCCT		intron_variant	Intron 13 of 52	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.2144+10_2144+21delTCCTTCCTTCCT		intron_variant	Intron 12 of 51	1		ENSP00000367079.3
ACACB	ENST00000377854.9	c.-1859+10_-1859+21delTCCTTCCTTCCT		intron_variant	Intron 12 of 46	5		ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.103 AC: 10798 AN: 104926 Hom.: 681 Cov.: 0

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0511

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.0384

Gnomad SAS AF: 0.0644

Gnomad FIN AF: 0.0685

Gnomad MID AF: 0.0776

Gnomad NFE AF: 0.0868

Gnomad OTH AF: 0.0980

GnomAD2 exomes AF: 0.0241 AC: 4504 AN: 187034 AF XY: 0.0216

Gnomad AFR exome AF: 0.0687

Gnomad AMR exome AF: 0.0173

Gnomad ASJ exome AF: 0.0171

Gnomad EAS exome AF: 0.0150

Gnomad FIN exome AF: 0.0383

Gnomad NFE exome AF: 0.0213

Gnomad OTH exome AF: 0.0294

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0277 AC: 34462 AN: 1243822 Hom.: 1633 AF XY: 0.0291 AC XY: 17868 AN XY: 613464

African (AFR) AF: 0.0752 AC: 2093 AN: 27824

American (AMR) AF: 0.0271 AC: 970 AN: 35752

Ashkenazi Jewish (ASJ) AF: 0.0433 AC: 943 AN: 21774

East Asian (EAS) AF: 0.0471 AC: 1544 AN: 32800

South Asian (SAS) AF: 0.0329 AC: 2324 AN: 70584

European-Finnish (FIN) AF: 0.0660 AC: 2921 AN: 44272

Middle Eastern (MID) AF: 0.0450 AC: 196 AN: 4360

European-Non Finnish (NFE) AF: 0.0224 AC: 21448 AN: 956256

Other (OTH) AF: 0.0403 AC: 2023 AN: 50200

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.103 AC: 10822 AN: 105014 Hom.: 684 Cov.: 0 AF XY: 0.102 AC XY: 5061 AN XY: 49672

African (AFR) AF: 0.169 AC: 4713 AN: 27856

American (AMR) AF: 0.0640 AC: 645 AN: 10076

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 220 AN: 2696

East Asian (EAS) AF: 0.0383 AC: 124 AN: 3240

South Asian (SAS) AF: 0.0650 AC: 158 AN: 2430

European-Finnish (FIN) AF: 0.0685 AC: 450 AN: 6566

Middle Eastern (MID) AF: 0.0762 AC: 16 AN: 210

European-Non Finnish (NFE) AF: 0.0867 AC: 4333 AN: 49964

Other (OTH) AF: 0.0977 AC: 130 AN: 1330

Alfa AF: 0.0479 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;