Variant rs2300455 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP4_StrongBA1

The NM_001093.4(ACACB):c.1951G>A(p.Ala651Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,610,442 control chromosomes in the GnomAD database, including 29,893 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.15 ( 2121 hom., cov: 31)

Exomes 𝑓: 0.19 ( 27772 hom. )

Consequence

ACACB
NM_001093.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.13

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ACACB. . Gene score misZ 1.5694 (greater than the threshold 3.09). Trascript score misZ 3.0917 (greater than threshold 3.09). GenCC has associacion of gene with isolated cleft palate.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026296377).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACACB	NM_001093.4 linkuse as main transcript	c.1951G>A	p.Ala651Thr	missense_variant	12/53	ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12 linkuse as main transcript	c.1951G>A	p.Ala651Thr	missense_variant	12/53	1	NM_001093.4	ENSP00000341044	P1	O00763-1
ACACB	ENST00000377848.7 linkuse as main transcript	c.1951G>A	p.Ala651Thr	missense_variant	11/52	1		ENSP00000367079	P1	O00763-1
ACACB	ENST00000377854.9 linkuse as main transcript	c.-2052G>A		5_prime_UTR_variant	11/47	5		ENSP00000367085

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22893

AN:

151788

Hom.:

2119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0389

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.154

GnomAD3 exomes

AF:

0.189

AC:

47034

AN:

248896

Hom.:

4863

AF XY:

0.193

AC XY:

26004

AN XY:

134584

show subpopulations

Gnomad AFR exome

AF:

0.0366

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.275

Gnomad SAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.195

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.192

AC:

280110

AN:

1458536

Hom.:

27772

Cov.:

AF XY:

0.193

AC XY:

140255

AN XY:

725190

show subpopulations

Gnomad4 AFR exome

AF:

0.0309

Gnomad4 AMR exome

AF:

0.164

Gnomad4 ASJ exome

AF:

0.212

Gnomad4 EAS exome

AF:

0.269

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.194

Gnomad4 OTH exome

AF:

0.187

GnomAD4 genome

AF:

0.151

AC:

22893

AN:

151906

Hom.:

2121

Cov.:

AF XY:

0.152

AC XY:

11256

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.0388

Gnomad4 AMR

AF:

0.165

Gnomad4 ASJ

AF:

0.210

Gnomad4 EAS

AF:

0.278

Gnomad4 SAS

AF:

0.228

Gnomad4 FIN

AF:

0.168

Gnomad4 NFE

AF:

0.194

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.181

Hom.:

4585

Bravo

AF:

0.143

TwinsUK

AF:

0.203

AC:

754

ALSPAC

AF:

0.202

AC:

777

ESP6500AA

AF:

0.0449

AC:

198

ESP6500EA

AF:

0.198

AC:

1704

ExAC

AF:

0.189

AC:

22901

Asia WGS

AF:

0.239

AC:

830

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.82

D;D

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

.;D

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-1.3

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

5.7e-9

P;P;P

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.57

Sift

Benign

0.052

T;T

Sift4G

Uncertain

0.048

D;D

Polyphen

1.0

D;D

Vest4

0.19

MPC

0.48

ClinPred

0.018

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.57

gMVP

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over