Genetic Variant ACACB:c.2144+61_2144+72dupTTCCTTCCTTCC (chr12-109188171-C-CTCCTTCCTTCCT) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001093.4(ACACB):c.2144+61_2144+72dupTTCCTTCCTTCC 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 3 hom., cov: 0)

Exomes 𝑓: 0.00041 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

ACACB
NM_001093.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 12-109188171-C-CTCCTTCCTTCCT is Benign according to our data. Variant chr12-109188171-C-CTCCTTCCTTCCT is described in ClinVar as Likely_benign. ClinVar VariationId is 2049236.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4 link	c.2144+61_2144+72dupTTCCTTCCTTCC		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+10insTCCTTCCTTCCT	intron_variant	Intron 13 of 52	1	NM_001093.4	ENSP00000341044.7	O00763-1
ACACB	ENST00000377848.7 link	c.2144+9_2144+10insTCCTTCCTTCCT	intron_variant	Intron 12 of 51	1		ENSP00000367079.3	O00763-1
ACACB	ENST00000377854.9 link	c.-1859+9_-1859+10insTCCTTCCTTCCT	intron_variant	Intron 12 of 46	5		ENSP00000367085.6	F8W8T8

Frequencies

GnomAD3 genomes

AF:

0.00189

AC:

199

AN:

105040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00475

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00522

Gnomad SAS

AF:

0.000824

Gnomad FIN

AF:

0.00152

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000300

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000407

AC:

509

AN:

1251962

Hom.:

Cov.:

AF XY:

0.000426

AC XY:

263

AN XY:

617858

show subpopulations

African (AFR)

AF:

0.00172

AC:

AN:

27902

American (AMR)

AF:

0.00120

AC:

AN:

35894

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21920

East Asian (EAS)

AF:

0.00570

AC:

189

AN:

33172

South Asian (SAS)

AF:

0.00108

AC:

AN:

71436

European-Finnish (FIN)

AF:

0.000420

AC:

AN:

45272

Middle Eastern (MID)

AF:

0.000452

AC:

AN:

4420

European-Non Finnish (NFE)

AF:

0.0000978

AC:

AN:

961364

Other (OTH)

AF:

0.000731

AC:

AN:

50582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

103

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00190

AC:

200

AN:

105130

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

AN XY:

49728

show subpopulations

African (AFR)

AF:

0.00477

AC:

133

AN:

27904

American (AMR)

AF:

0.00228

AC:

AN:

10076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2698

East Asian (EAS)

AF:

0.00524

AC:

AN:

3246

South Asian (SAS)

AF:

0.000822

AC:

AN:

2432

European-Finnish (FIN)

AF:

0.00152

AC:

AN:

6572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

210

European-Non Finnish (NFE)

AF:

0.000300

AC:

AN:

50016

Other (OTH)

AF:

0.00

AC:

AN:

1330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 21, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

(source)

Splicing

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

Publications

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12-109188171-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT-CTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over