Genetic Variant ACACB:c.2144+45_2144+72delTTCCTTCCTTCCTTCCTTCCTTCCTTCC (chr12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCTTCCT-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001093.4(ACACB):c.2144+45_2144+72delTTCCTTCCTTCCTTCCTTCCTTCCTTCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,357,116 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ACACB
NM_001093.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.21

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4 link	c.2144+45_2144+72delTTCCTTCCTTCCTTCCTTCCTTCCTTCC		intron_variant	Intron 13 of 52	ENST00000338432.12	NP_001084.3	O00763-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACACB	ENST00000338432.12 link	c.2144+10_2144+37delTCCTTCCTTCCTTCCTTCCTTCCTTCCT	intron_variant	Intron 13 of 52	1	NM_001093.4	ENSP00000341044.7	O00763-1
ACACB	ENST00000377848.7 link	c.2144+10_2144+37delTCCTTCCTTCCTTCCTTCCTTCCTTCCT	intron_variant	Intron 12 of 51	1		ENSP00000367079.3	O00763-1
ACACB	ENST00000377854.9 link	c.-1859+10_-1859+37delTCCTTCCTTCCTTCCTTCCTTCCTTCCT	intron_variant	Intron 12 of 46	5		ENSP00000367085.6	F8W8T8

Frequencies

GnomAD3 genomes

AF:

0.000438

AC:

AN:

105050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000298

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000307

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000180

Gnomad OTH

AF:

0.00152

GnomAD4 exome

AF:

0.000139

AC:

174

AN:

1251976

Hom.:

AF XY:

0.000175

AC XY:

108

AN XY:

617868

show subpopulations

African (AFR)

AF:

0.00136

AC:

AN:

27904

American (AMR)

AF:

0.000446

AC:

AN:

35894

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21920

East Asian (EAS)

AF:

0.0000301

AC:

AN:

33178

South Asian (SAS)

AF:

0.000126

AC:

AN:

71436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45274

Middle Eastern (MID)

AF:

0.00249

AC:

AN:

4420

European-Non Finnish (NFE)

AF:

0.0000895

AC:

AN:

961368

Other (OTH)

AF:

0.000257

AC:

AN:

50582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.577

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000438

AC:

AN:

105140

Hom.:

Cov.:

AF XY:

0.000462

AC XY:

AN XY:

49734

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

27910

American (AMR)

AF:

0.000298

AC:

AN:

10078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2698

East Asian (EAS)

AF:

0.000308

AC:

AN:

3246

South Asian (SAS)

AF:

0.00

AC:

AN:

2432

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

210

European-Non Finnish (NFE)

AF:

0.000180

AC:

AN:

50016

Other (OTH)

AF:

0.00150

AC:

AN:

1330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.590

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

759

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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