Genetic Variant ACACB:c.2144+37_2144+72dupTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCC (chr12-109188171-C-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT) – 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+37_2144+72dupTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_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 0.0000095 ( 0 hom., cov: 0)

Consequence

ACACB
NM_001093.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.839

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+37_2144+72dupTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCC		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+9_2144+10insTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT	intron_variant	Intron 13 of 52	1	NM_001093.4	ENSP00000341044.7	O00763-1
ACACB	ENST00000377848.7 link	c.2144+9_2144+10insTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT	intron_variant	Intron 12 of 51	1		ENSP00000367079.3	O00763-1
ACACB	ENST00000377854.9 link	c.-1859+9_-1859+10insTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT	intron_variant	Intron 12 of 46	5		ENSP00000367085.6	F8W8T8

Frequencies

GnomAD3 genomes

AF:

0.00000952

AC:

AN:

105050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000360

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000952

AC:

AN:

105050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

49634

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000360

AC:

AN:

27812

American (AMR)

AF:

0.00

AC:

AN:

10064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2698

East Asian (EAS)

AF:

0.00

AC:

AN:

3258

South Asian (SAS)

AF:

0.00

AC:

AN:

2426

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

50024

Other (OTH)

AF:

0.00

AC:

AN:

1316

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.84

Splicing

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

Publications

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12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over