Variant rs2878960 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000338432.12(ACACB):c.525C>T(p.Ser175=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,613,780 control chromosomes in the GnomAD database, including 319,608 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 0.52 ( 23075 hom., cov: 32)

Exomes 𝑓: 0.63 ( 296533 hom. )

Consequence

ACACB
ENST00000338432.12 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.98

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP7

Synonymous conserved (PhyloP=-2.98 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 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.525C>T	p.Ser175=	synonymous_variant	2/53	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.525C>T	p.Ser175=	synonymous_variant	2/53	1	NM_001093.4	ENSP00000341044	P1	O00763-1

Frequencies

GnomAD3 genomes

AF:

0.524

AC:

79701

AN:

151966

Hom.:

23084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.701

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.491

Gnomad FIN

AF:

0.660

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.669

Gnomad OTH

AF:

0.564

GnomAD3 exomes

AF:

0.553

AC:

138337

AN:

250234

Hom.:

41507

AF XY:

0.567

AC XY:

76824

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.296

Gnomad AMR exome

AF:

0.375

Gnomad ASJ exome

AF:

0.640

Gnomad EAS exome

AF:

0.256

Gnomad SAS exome

AF:

0.510

Gnomad FIN exome

AF:

0.666

Gnomad NFE exome

AF:

0.672

Gnomad OTH exome

AF:

0.609

GnomAD4 exome

AF:

0.628

AC:

917292

AN:

1461696

Hom.:

296533

Cov.:

AF XY:

0.627

AC XY:

456239

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.290

Gnomad4 AMR exome

AF:

0.384

Gnomad4 ASJ exome

AF:

0.638

Gnomad4 EAS exome

AF:

0.228

Gnomad4 SAS exome

AF:

0.517

Gnomad4 FIN exome

AF:

0.661

Gnomad4 NFE exome

AF:

0.669

Gnomad4 OTH exome

AF:

0.608

GnomAD4 genome

AF:

0.524

AC:

79686

AN:

152084

Hom.:

23075

Cov.:

AF XY:

0.520

AC XY:

38691

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.296

Gnomad4 AMR

AF:

0.462

Gnomad4 ASJ

AF:

0.638

Gnomad4 EAS

AF:

0.252

Gnomad4 SAS

AF:

0.491

Gnomad4 FIN

AF:

0.660

Gnomad4 NFE

AF:

0.669

Gnomad4 OTH

AF:

0.560

Alfa

AF:

0.635

Hom.:

60678

Bravo

AF:

0.500

Asia WGS

AF:

0.372

AC:

1290

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.076

DANN

Benign

0.60

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