dbSNP rs35724886: ACOT4:p.Ala187Asp (chr14-73593804-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_152331.4(ACOT4):c.560C>A(p.Ala187Asp) variant causes a missense change. The variant allele was found at a frequency of 0.186 in 1,607,944 control chromosomes in the GnomAD database, including 32,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 2210 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29806 hom. )

Consequence

ACOT4
NM_152331.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.17

Publications

19 publications found

Variant links:

Genes affected

ACOT4 (HGNC:19748): (acyl-CoA thioesterase 4) Enables acyl-CoA hydrolase activity and succinyl-CoA hydrolase activity. Involved in carboxylic acid metabolic process; saturated monocarboxylic acid metabolic process; and succinyl-CoA metabolic process. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ACOT4 links:

ENSG00000258603 (HGNC:):

ENSG00000258603 links:

HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

HEATR4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026230812).

BP6

Variant 14-73593804-C-A is Benign according to our data. Variant chr14-73593804-C-A is described in ClinVar as Benign. ClinVar VariationId is 2798877.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACOT4	NM_152331.4 link	c.560C>A	p.Ala187Asp	missense_variant	Exon 2 of 3	ENST00000326303.5	NP_689544.3	Q8N9L9
HEATR4	XM_047431370.1 link	c.-73+39857G>T		intron_variant	Intron 1 of 16		XP_047287326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOT4	ENST00000326303.5 link	c.560C>A	p.Ala187Asp	missense_variant	Exon 2 of 3	1	NM_152331.4	ENSP00000323071.4		Q8N9L9

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22370

AN:

152052

Hom.:

2209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0524

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.00346

Gnomad SAS

AF:

0.0652

Gnomad FIN

AF:

0.260

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.136

GnomAD2 exomes

AF:

0.0495

AC:

10293

AN:

207986

AF XY:

0.0491

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.0153

Gnomad ASJ exome

AF:

0.0319

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.0743

Gnomad OTH exome

AF:

0.0452

GnomAD4 exome

AF:

0.190

AC:

277149

AN:

1455774

Hom.:

29806

Cov.:

AF XY:

0.186

AC XY:

134915

AN XY:

723760

show subpopulations

African (AFR)

AF:

0.0453

AC:

1512

AN:

33360

American (AMR)

AF:

0.0867

AC:

3836

AN:

44266

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2860

AN:

25964

East Asian (EAS)

AF:

0.000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0723

AC:

6196

AN:

85754

European-Finnish (FIN)

AF:

0.253

AC:

13450

AN:

53146

Middle Eastern (MID)

AF:

0.0576

AC:

332

AN:

5762

European-Non Finnish (NFE)

AF:

0.216

AC:

239115

AN:

1107676

Other (OTH)

AF:

0.163

AC:

9828

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

10617

21233

31850

42466

53083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7948

15896

23844

31792

39740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.147

AC:

22371

AN:

152170

Hom.:

2210

Cov.:

AF XY:

0.145

AC XY:

10827

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0523

AC:

2173

AN:

41562

American (AMR)

AF:

0.107

AC:

1639

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

409

AN:

3472

East Asian (EAS)

AF:

0.00347

AC:

AN:

5188

South Asian (SAS)

AF:

0.0654

AC:

315

AN:

4814

European-Finnish (FIN)

AF:

0.260

AC:

2743

AN:

10568

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.215

AC:

14638

AN:

67970

Other (OTH)

AF:

0.134

AC:

283

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

858

1717

2575

3434

4292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0548

Hom.:

1425

Bravo

AF:

0.133

ESP6500AA

AF:

0.0172

AC:

ESP6500EA

AF:

0.0974

AC:

837

ExAC

AF:

0.128

AC:

15546

Asia WGS

AF:

0.0330

AC:

115

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.91

MutationAssessor

Pathogenic

3.7

PhyloP100

4.2

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.6

REVEL

Uncertain

0.33

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.34

MPC

1.1

ClinPred

0.074

GERP RS

5.3

Varity_R

0.95

gMVP

0.95

Mutation Taster

=86/14

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over