Genetic Variant ACACB:c.2144+49_2144+72delTTCCTTCCTTCCTTCCTTCCTTCC (chr12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCT-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+49_2144+72delTTCCTTCCTTCCTTCCTTCCTTCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,357,102 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.0010 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00020 ( 1 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:

Genome browser will be placed here

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+49_2144+72delTTCCTTCCTTCCTTCCTTCCTTCC		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+33delTCCTTCCTTCCTTCCTTCCTTCCT	intron_variant	Intron 13 of 52	1	NM_001093.4	ENSP00000341044.7	O00763-1
ACACB	ENST00000377848.7 link	c.2144+10_2144+33delTCCTTCCTTCCTTCCTTCCTTCCT	intron_variant	Intron 12 of 51	1		ENSP00000367079.3	O00763-1
ACACB	ENST00000377854.9 link	c.-1859+10_-1859+33delTCCTTCCTTCCTTCCTTCCTTCCT	intron_variant	Intron 12 of 46	5		ENSP00000367085.6	F8W8T8

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

110

AN:

105048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00320

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000994

Gnomad ASJ

AF:

0.000371

Gnomad EAS

AF:

0.000614

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000152

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000300

Gnomad OTH

AF:

0.000760

GnomAD4 exome

AF:

0.000199

AC:

249

AN:

1251964

Hom.:

AF XY:

0.000172

AC XY:

106

AN XY:

617864

show subpopulations

African (AFR)

AF:

0.00229

AC:

AN:

27900

American (AMR)

AF:

0.000111

AC:

AN:

35894

Ashkenazi Jewish (ASJ)

AF:

0.0000912

AC:

AN:

21920

East Asian (EAS)

AF:

0.000301

AC:

AN:

33178

South Asian (SAS)

AF:

0.0000980

AC:

AN:

71434

European-Finnish (FIN)

AF:

0.000155

AC:

AN:

45274

Middle Eastern (MID)

AF:

0.000679

AC:

AN:

4420

European-Non Finnish (NFE)

AF:

0.000144

AC:

138

AN:

961362

Other (OTH)

AF:

0.000277

AC:

AN:

50582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.566

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00105

AC:

110

AN:

105138

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

49732

show subpopulations

African (AFR)

AF:

0.00319

AC:

AN:

27908

American (AMR)

AF:

0.0000992

AC:

AN:

10078

Ashkenazi Jewish (ASJ)

AF:

0.000371

AC:

AN:

2698

East Asian (EAS)

AF:

0.000616

AC:

AN:

3246

South Asian (SAS)

AF:

0.00

AC:

AN:

2432

European-Finnish (FIN)

AF:

0.000152

AC:

AN:

6574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

210

European-Non Finnish (NFE)

AF:

0.000300

AC:

AN:

50016

Other (OTH)

AF:

0.000752

AC:

AN:

1330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.569

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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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12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT-CTCCTTCCTTCCTTCCT

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