dbSNP rs3742023: ACACB:p.His2068His (chr12-109256177-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.6204C>T(p.His2068His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,612,772 control chromosomes in the GnomAD database, including 100,135 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 0.30 ( 7611 hom., cov: 32)

Exomes 𝑓: 0.35 ( 92524 hom. )

Consequence

ACACB
NM_001093.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.560

Publications

32 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=-0.62).

BP7

Synonymous conserved (PhyloP=-0.56 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACACB	NM_001093.4 link	c.6204C>T	p.His2068His	synonymous_variant	Exon 45 of 53	ENST00000338432.12	NP_001084.3	O00763-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACACB	ENST00000338432.12 link	c.6204C>T	p.His2068His	synonymous_variant	Exon 45 of 53	1	NM_001093.4	ENSP00000341044.7	O00763-1
ACACB	ENST00000377848.7 link	c.6204C>T	p.His2068His	synonymous_variant	Exon 44 of 52	1		ENSP00000367079.3	O00763-1
ACACB	ENST00000377854.9 link	c.2202C>T	p.His734His	synonymous_variant	Exon 44 of 47	5		ENSP00000367085.6	F8W8T8
ACACB	ENST00000538526.5 link	n.2202C>T		non_coding_transcript_exon_variant	Exon 17 of 26	5		ENSP00000443281.1	H0YGH5

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45496

AN:

151834

Hom.:

7610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.448

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.360

Gnomad OTH

AF:

0.299

GnomAD2 exomes

AF:

0.333

AC:

83594

AN:

250862

AF XY:

0.336

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.356

Gnomad ASJ exome

AF:

0.318

Gnomad EAS exome

AF:

0.271

Gnomad FIN exome

AF:

0.435

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.347

GnomAD4 exome

AF:

0.352

AC:

514176

AN:

1460820

Hom.:

92524

Cov.:

AF XY:

0.351

AC XY:

255224

AN XY:

726790

show subpopulations

African (AFR)

AF:

0.144

AC:

4807

AN:

33470

American (AMR)

AF:

0.350

AC:

15636

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

8383

AN:

26116

East Asian (EAS)

AF:

0.328

AC:

13013

AN:

39686

South Asian (SAS)

AF:

0.298

AC:

25723

AN:

86220

European-Finnish (FIN)

AF:

0.430

AC:

22950

AN:

53336

Middle Eastern (MID)

AF:

0.276

AC:

1594

AN:

5768

European-Non Finnish (NFE)

AF:

0.362

AC:

401758

AN:

1111170

Other (OTH)

AF:

0.337

AC:

20312

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

16334

32668

49003

65337

81671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12706

25412

38118

50824

63530

<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:

0.299

AC:

45509

AN:

151952

Hom.:

7611

Cov.:

AF XY:

0.305

AC XY:

22616

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.153

AC:

6338

AN:

41458

American (AMR)

AF:

0.326

AC:

4984

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

1149

AN:

3468

East Asian (EAS)

AF:

0.292

AC:

1504

AN:

5146

South Asian (SAS)

AF:

0.296

AC:

1426

AN:

4816

European-Finnish (FIN)

AF:

0.448

AC:

4721

AN:

10548

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.360

AC:

24472

AN:

67934

Other (OTH)

AF:

0.301

AC:

635

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1559

3118

4676

6235

7794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.338

Hom.:

18451

Bravo

AF:

0.284

Asia WGS

AF:

0.298

AC:

1038

AN:

3478

EpiCase

AF:

0.344

EpiControl

AF:

0.346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.4

(source)

DANN

Benign

0.70

PhyloP100

-0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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