chr12-109188171-C-CTCCT

Variant names:

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

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+69_2144+72dupTTCC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (195 hom., cov: 0)
  • Exomes 𝑓: 0.017 (256 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACACB NM_001093.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.839
• 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-C-CTCCT is Benign according to our data. Variant chr12-109188171-C-CTCCT is described in ClinVar as Benign. ClinVar VariationId is 769831.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+69_2144+72dupTTCC		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+9_2144+10insTCCT		intron_variant	Intron 13 of 52	1	NM_001093.4	ENSP00000341044.7
ACACB	ENST00000377848.7	c.2144+9_2144+10insTCCT		intron_variant	Intron 12 of 51	1		ENSP00000367079.3
ACACB	ENST00000377854.9	c.-1859+9_-1859+10insTCCT		intron_variant	Intron 12 of 46	5		ENSP00000367085.6

Frequencies

GnomAD3 genomes AF: 0.0523 AC: 5489 AN: 104908 Hom.: 195 Cov.: 0

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0747

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0517

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.0623

GnomAD2 exomes AF: 0.0130 AC: 2435 AN: 187034 AF XY: 0.0113

Gnomad AFR exome AF: 0.0134

Gnomad AMR exome AF: 0.0277

Gnomad ASJ exome AF: 0.00785

Gnomad EAS exome AF: 0.0261

Gnomad FIN exome AF: 0.00851

Gnomad NFE exome AF: 0.00931

Gnomad OTH exome AF: 0.0188

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0166 AC: 20827 AN: 1251184 Hom.: 256 Cov.: 0 AF XY: 0.0179 AC XY: 11053 AN XY: 617468

African (AFR) AF: 0.0177 AC: 493 AN: 27892

American (AMR) AF: 0.0428 AC: 1533 AN: 35838

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 731 AN: 21892

East Asian (EAS) AF: 0.0602 AC: 1994 AN: 33110

South Asian (SAS) AF: 0.0266 AC: 1898 AN: 71394

European-Finnish (FIN) AF: 0.0275 AC: 1242 AN: 45196

Middle Eastern (MID) AF: 0.0240 AC: 106 AN: 4418

European-Non Finnish (NFE) AF: 0.0120 AC: 11550 AN: 960928

Other (OTH) AF: 0.0253 AC: 1280 AN: 50516

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0524 AC: 5498 AN: 104998 Hom.: 195 Cov.: 0 AF XY: 0.0508 AC XY: 2523 AN XY: 49666

African (AFR) AF: 0.0405 AC: 1128 AN: 27868

American (AMR) AF: 0.0841 AC: 846 AN: 10056

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 139 AN: 2696

East Asian (EAS) AF: 0.0746 AC: 242 AN: 3242

South Asian (SAS) AF: 0.0535 AC: 130 AN: 2428

European-Finnish (FIN) AF: 0.0314 AC: 206 AN: 6570

Middle Eastern (MID) AF: 0.0476 AC: 10 AN: 210

European-Non Finnish (NFE) AF: 0.0522 AC: 2606 AN: 49954

Other (OTH) AF: 0.0624 AC: 83 AN: 1330

Alfa AF: 0.0294 Hom.: 759

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 13, 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		0.84
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: COSV58142486; COSMIC: COSV58142486;