Genetic Variant ACACB:p.Ala272Ala (chr12-109167925-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001093.4(ACACB):c.816C>T(p.Ala272Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,613,306 control chromosomes in the GnomAD database, including 36,864 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 3042 hom., cov: 28)

Exomes 𝑓: 0.21 ( 33822 hom. )

Consequence

ACACB
NM_001093.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.89

Publications

16 publications found

Variant links:

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)

ACACB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP7

Synonymous conserved (PhyloP=-2.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4 link	c.816C>T	p.Ala272Ala	synonymous_variant	Exon 4 of 53	ENST00000338432.12	NP_001084.3	O00763-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12 link	c.816C>T	p.Ala272Ala	synonymous_variant	Exon 4 of 53	1	NM_001093.4	ENSP00000341044.7		O00763-1

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27191

AN:

151610

Hom.:

3039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0709

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.183

GnomAD2 exomes

AF:

0.233

AC:

58490

AN:

251142

AF XY:

0.233

show subpopulations

Gnomad AFR exome

AF:

0.0690

Gnomad AMR exome

AF:

0.260

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.549

Gnomad FIN exome

AF:

0.218

Gnomad NFE exome

AF:

0.195

Gnomad OTH exome

AF:

0.216

GnomAD4 exome

AF:

0.206

AC:

301470

AN:

1461578

Hom.:

33822

Cov.:

AF XY:

0.208

AC XY:

150888

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.0638

AC:

2136

AN:

33476

American (AMR)

AF:

0.251

AC:

11229

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

6073

AN:

26130

East Asian (EAS)

AF:

0.507

AC:

20114

AN:

39638

South Asian (SAS)

AF:

0.251

AC:

21649

AN:

86250

European-Finnish (FIN)

AF:

0.219

AC:

11677

AN:

53414

Middle Eastern (MID)

AF:

0.144

AC:

828

AN:

5764

European-Non Finnish (NFE)

AF:

0.194

AC:

215175

AN:

1111862

Other (OTH)

AF:

0.209

AC:

12589

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

12988

25976

38963

51951

64939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7706

15412

23118

30824

38530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.179

AC:

27204

AN:

151728

Hom.:

3042

Cov.:

AF XY:

0.184

AC XY:

13634

AN XY:

74096

show subpopulations

African (AFR)

AF:

0.0708

AC:

2931

AN:

41402

American (AMR)

AF:

0.217

AC:

3295

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

818

AN:

3470

East Asian (EAS)

AF:

0.529

AC:

2691

AN:

5084

South Asian (SAS)

AF:

0.265

AC:

1268

AN:

4792

European-Finnish (FIN)

AF:

0.221

AC:

2329

AN:

10538

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.195

AC:

13239

AN:

67914

Other (OTH)

AF:

0.186

AC:

392

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

956

1911

2867

3822

4778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.183

Hom.:

1727

Bravo

AF:

0.175

Asia WGS

AF:

0.346

AC:

1205

AN:

3478

EpiCase

AF:

0.189

EpiControl

AF:

0.191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.32

(source)

DANN

Benign

0.64

PhyloP100

-2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=78/22

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over