Variant rs3742026 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001093.4(ACACB):c.4139+46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,606,722 control chromosomes in the GnomAD database, including 109,431 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 0.34 ( 9496 hom., cov: 32)

Exomes 𝑓: 0.37 ( 99935 hom. )

Consequence

ACACB
NM_001093.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.79

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.424 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.4139+46G>C		intron_variant		ENST00000338432.12	NP_001084.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ACACB	ENST00000338432.12 linkuse as main transcript	c.4139+46G>C	intron_variant	1	NM_001093.4	ENSP00000341044	P1	O00763-1
ACACB	ENST00000377848.7 linkuse as main transcript	c.4139+46G>C	intron_variant	1		ENSP00000367079	P1	O00763-1
ACACB	ENST00000377854.9 linkuse as main transcript	c.137+46G>C	intron_variant	5		ENSP00000367085
ACACB	ENST00000538526.5 linkuse as main transcript	c.138+46G>C	intron_variant, NMD_transcript_variant	5		ENSP00000443281

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52422

AN:

151884

Hom.:

9506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.433

Gnomad ASJ

AF:

0.415

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.365

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.382

GnomAD3 exomes

AF:

0.385

AC:

93772

AN:

243756

Hom.:

18547

AF XY:

0.383

AC XY:

50354

AN XY:

131532

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.494

Gnomad ASJ exome

AF:

0.431

Gnomad EAS exome

AF:

0.424

Gnomad SAS exome

AF:

0.371

Gnomad FIN exome

AF:

0.327

Gnomad NFE exome

AF:

0.373

Gnomad OTH exome

AF:

0.383

GnomAD4 exome

AF:

0.368

AC:

535131

AN:

1454720

Hom.:

99935

Cov.:

AF XY:

0.368

AC XY:

265980

AN XY:

723132

show subpopulations

Gnomad4 AFR exome

AF:

0.259

Gnomad4 AMR exome

AF:

0.496

Gnomad4 ASJ exome

AF:

0.430

Gnomad4 EAS exome

AF:

0.356

Gnomad4 SAS exome

AF:

0.370

Gnomad4 FIN exome

AF:

0.329

Gnomad4 NFE exome

AF:

0.366

Gnomad4 OTH exome

AF:

0.368

GnomAD4 genome

AF:

0.345

AC:

52405

AN:

152002

Hom.:

9496

Cov.:

AF XY:

0.342

AC XY:

25448

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.262

Gnomad4 AMR

AF:

0.433

Gnomad4 ASJ

AF:

0.415

Gnomad4 EAS

AF:

0.400

Gnomad4 SAS

AF:

0.365

Gnomad4 FIN

AF:

0.324

Gnomad4 NFE

AF:

0.367

Gnomad4 OTH

AF:

0.381

Alfa

AF:

0.357

Hom.:

1800

Bravo

AF:

0.356

Asia WGS

AF:

0.344

AC:

1196

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.065

DANN

Benign

0.79

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