Variant rs25683 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005891.3(ACAT2):c.632A>G(p.Lys211Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,613,274 control chromosomes in the GnomAD database, including 246,688 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.46 ( 18101 hom., cov: 32)

Exomes 𝑓: 0.55 ( 228587 hom. )

Consequence

ACAT2
NM_005891.3 missense, splice_region

Scores

Splicing: ADA: 0.2030

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.65

Variant links:

Genes affected

ACAT2 (HGNC:94): (acetyl-CoA acetyltransferase 2) The product of this gene is an enzyme involved in lipid metabolism, and it encodes cytosolic acetoacetyl-CoA thiolase. This gene shows complementary overlapping with the 3-prime region of the TCP1 gene in both mouse and human. These genes are encoded on opposite strands of DNA, as well as in opposite transcriptional orientation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

ACAT2 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 (MetaRNN=8.2847476E-4).

BP6

Variant 6-159775311-A-G is Benign according to our data. Variant chr6-159775311-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACAT2	NM_005891.3 linkuse as main transcript	c.632A>G	p.Lys211Arg	missense_variant, splice_region_variant	5/9	ENST00000367048.5
ACAT2	NM_001303253.1 linkuse as main transcript	c.719A>G	p.Lys240Arg	missense_variant, splice_region_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACAT2	ENST00000367048.5 linkuse as main transcript	c.632A>G	p.Lys211Arg	missense_variant, splice_region_variant	5/9	1	NM_005891.3	P1	Q9BWD1-1
ACAT2	ENST00000472052.1 linkuse as main transcript	n.26A>G		non_coding_transcript_exon_variant	1/4	2
ACAT2	ENST00000467951.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69592

AN:

151968

Hom.:

18094

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.578

Gnomad OTH

AF:

0.463

GnomAD3 exomes

AF:

0.522

AC:

131212

AN:

251198

Hom.:

36777

AF XY:

0.524

AC XY:

71213

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.639

Gnomad ASJ exome

AF:

0.557

Gnomad EAS exome

AF:

0.184

Gnomad SAS exome

AF:

0.501

Gnomad FIN exome

AF:

0.573

Gnomad NFE exome

AF:

0.578

Gnomad OTH exome

AF:

0.546

GnomAD4 exome

AF:

0.552

AC:

806837

AN:

1461186

Hom.:

228587

Cov.:

AF XY:

0.550

AC XY:

399827

AN XY:

726912

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.632

Gnomad4 ASJ exome

AF:

0.554

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.502

Gnomad4 FIN exome

AF:

0.580

Gnomad4 NFE exome

AF:

0.577

Gnomad4 OTH exome

AF:

0.516

GnomAD4 genome

AF:

0.458

AC:

69593

AN:

152088

Hom.:

18101

Cov.:

AF XY:

0.456

AC XY:

33915

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.545

Gnomad4 ASJ

AF:

0.563

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.496

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.578

Gnomad4 OTH

AF:

0.458

Alfa

AF:

0.546

Hom.:

57471

Bravo

AF:

0.445

TwinsUK

AF:

0.566

AC:

2100

ALSPAC

AF:

0.558

AC:

2150

ESP6500AA

AF:

0.220

AC:

969

ESP6500EA

AF:

0.574

AC:

4940

ExAC

AF:

0.516

AC:

62606

Asia WGS

AF:

0.352

AC:

1226

AN:

3478

EpiCase

AF:

0.571

EpiControl

AF:

0.572

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.77

MetaRNN

Benign

0.00083

MetaSVM

Uncertain

0.43

MutationAssessor

Benign

1.5

MutationTaster

Benign

2.5e-8

P;P

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.58

Sift

Benign

0.043

Sift4G

Benign

0.14

Polyphen

0.92

Vest4

0.11

MPC

0.10

ClinPred

0.031

GERP RS

5.7

Varity_R

0.54

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.20

dbscSNV1_RF

Benign

0.28

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