12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT

Variant names:

• chr12-109188171-CTCCTTCCT-C
• rs373209583
• NM_001093.4:c.2144+65_2144+72delTTCCTTCC

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+65_2144+72delTTCCTTCC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (5208 hom., cov: 0)
  • Exomes 𝑓: 0.11 (19630 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-CTCCTTCCT-C is Benign according to our data. Variant chr12-109188171-CTCCTTCCT-C is described in ClinVar as Benign. ClinVar VariationId is 402333.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4	c.2144+65_2144+72delTTCCTTCC		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+17delTCCTTCCT		intron_variant	Intron 13 of 52	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.2144+10_2144+17delTCCTTCCT		intron_variant	Intron 12 of 51	1		ENSP00000367079.3
ACACB	ENST00000377854.9	c.-1859+10_-1859+17delTCCTTCCT		intron_variant	Intron 12 of 46	5		ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.296 AC: 31008 AN: 104784 Hom.: 5209 Cov.: 0

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.409

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.321

GnomAD2 exomes AF: 0.0866 AC: 16188 AN: 187034 AF XY: 0.0795

Gnomad AFR exome AF: 0.0587

Gnomad AMR exome AF: 0.0729

Gnomad ASJ exome AF: 0.0500

Gnomad EAS exome AF: 0.111

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.0858

Gnomad OTH exome AF: 0.105

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.106 AC: 131609 AN: 1244726 Hom.: 19630 AF XY: 0.113 AC XY: 69439 AN XY: 614048

African (AFR) AF: 0.0717 AC: 1994 AN: 27798

American (AMR) AF: 0.105 AC: 3753 AN: 35682

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3332 AN: 21684

East Asian (EAS) AF: 0.223 AC: 7317 AN: 32842

South Asian (SAS) AF: 0.183 AC: 12957 AN: 70864

European-Finnish (FIN) AF: 0.302 AC: 13487 AN: 44604

Middle Eastern (MID) AF: 0.175 AC: 768 AN: 4386

European-Non Finnish (NFE) AF: 0.0849 AC: 81208 AN: 956656

Other (OTH) AF: 0.135 AC: 6793 AN: 50210

GnomAD4 genome AF: 0.296 AC: 31021 AN: 104872 Hom.: 5208 Cov.: 0 AF XY: 0.295 AC XY: 14651 AN XY: 49622

African (AFR) AF: 0.170 AC: 4733 AN: 27838

American (AMR) AF: 0.245 AC: 2460 AN: 10050

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 748 AN: 2694

East Asian (EAS) AF: 0.298 AC: 965 AN: 3236

South Asian (SAS) AF: 0.311 AC: 754 AN: 2426

European-Finnish (FIN) AF: 0.402 AC: 2640 AN: 6566

Middle Eastern (MID) AF: 0.400 AC: 84 AN: 210

European-Non Finnish (NFE) AF: 0.361 AC: 17990 AN: 49884

Other (OTH) AF: 0.318 AC: 422 AN: 1328

Alfa AF: 0.225 Hom.: 759

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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; COSMIC: COSV58130966; COSMIC: COSV58130966;