Variant rs3742023 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001093.4(ACACB):c.6204C>T(p.His2068=) 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ACACB	NM_001093.4 linkuse as main transcript	c.6204C>T	p.His2068=	synonymous_variant	45/53	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.6204C>T	p.His2068=	synonymous_variant	45/53	1	NM_001093.4	ENSP00000341044	P1	O00763-1
ACACB	ENST00000377848.7 linkuse as main transcript	c.6204C>T	p.His2068=	synonymous_variant	44/52	1		ENSP00000367079	P1	O00763-1
ACACB	ENST00000377854.9 linkuse as main transcript	c.2202C>T	p.His734=	synonymous_variant	44/47	5		ENSP00000367085
ACACB	ENST00000538526.5 linkuse as main transcript	c.2205C>T	p.His735=	synonymous_variant, NMD_transcript_variant	17/26	5		ENSP00000443281

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

GnomAD3 exomes

AF:

0.333

AC:

83594

AN:

250862

Hom.:

14660

AF XY:

0.336

AC XY:

45538

AN XY:

135650

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 SAS exome

AF:

0.296

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

Gnomad4 AFR exome

AF:

0.144

Gnomad4 AMR exome

AF:

0.350

Gnomad4 ASJ exome

AF:

0.321

Gnomad4 EAS exome

AF:

0.328

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.430

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.337

GnomAD4 genome

AF:

0.299

AC:

45509

AN:

151952

Hom.:

7611

Cov.:

AF XY:

0.305

AC XY:

22616

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.326

Gnomad4 ASJ

AF:

0.331

Gnomad4 EAS

AF:

0.292

Gnomad4 SAS

AF:

0.296

Gnomad4 FIN

AF:

0.448

Gnomad4 NFE

AF:

0.360

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.342

Hom.:

15584

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

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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