Genetic Variant ACAA1:c.324-237G>A (chr3-38132242-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001607.4(ACAA1):c.324-237G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 327,298 control chromosomes in the GnomAD database, including 18,356 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 0.35 ( 10686 hom., cov: 32)

Exomes 𝑓: 0.29 ( 7670 hom. )

Consequence

ACAA1
NM_001607.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.627

Publications

19 publications found

Variant links:

Genes affected

ACAA1 (HGNC:82): (acetyl-CoA acyltransferase 1) This gene encodes an enzyme operative in the beta-oxidation system of the peroxisomes. Deficiency of this enzyme leads to pseudo-Zellweger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACAA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001607.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACAA1	NM_001607.4	MANE Select	c.324-237G>A	intron	N/A	NP_001598.1
ACAA1	NM_001130410.2		c.324-237G>A	intron	N/A	NP_001123882.1
ACAA1	NR_024024.2		n.416-237G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACAA1	ENST00000333167.13	TSL:1 MANE Select	c.324-237G>A	intron	N/A	ENSP00000333664.8
ACAA1	ENST00000301810.11	TSL:1	c.324-237G>A	intron	N/A	ENSP00000301810.7
ACAA1	ENST00000411549.5	TSL:1	n.324-237G>A	intron	N/A	ENSP00000414021.1

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53559

AN:

151954

Hom.:

10646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.561

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.330

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.348

GnomAD4 exome

AF:

0.294

AC:

51583

AN:

175226

Hom.:

7670

Cov.:

AF XY:

0.291

AC XY:

26841

AN XY:

92118

show subpopulations

African (AFR)

AF:

0.562

AC:

3679

AN:

6548

American (AMR)

AF:

0.286

AC:

2705

AN:

9448

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

1523

AN:

5450

East Asian (EAS)

AF:

0.343

AC:

4068

AN:

11858

South Asian (SAS)

AF:

0.258

AC:

4923

AN:

19048

European-Finnish (FIN)

AF:

0.269

AC:

2532

AN:

9418

Middle Eastern (MID)

AF:

0.381

AC:

297

AN:

780

European-Non Finnish (NFE)

AF:

0.281

AC:

28844

AN:

102570

Other (OTH)

AF:

0.298

AC:

3012

AN:

10106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1771

3542

5313

7084

8855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

266

532

798

1064

1330

<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:

0.353

AC:

53659

AN:

152072

Hom.:

10686

Cov.:

AF XY:

0.351

AC XY:

26118

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.562

AC:

23293

AN:

41440

American (AMR)

AF:

0.285

AC:

4352

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

904

AN:

3470

East Asian (EAS)

AF:

0.331

AC:

1705

AN:

5156

South Asian (SAS)

AF:

0.232

AC:

1121

AN:

4834

European-Finnish (FIN)

AF:

0.268

AC:

2836

AN:

10586

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18378

AN:

67976

Other (OTH)

AF:

0.348

AC:

735

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1689

3379

5068

6758

8447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.287

Hom.:

11252

Bravo

AF:

0.367

Asia WGS

AF:

0.295

AC:

1025

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.98

(source)

DANN

Benign

0.18

PhyloP100

-0.63

PromoterAI

-0.0032

Neutral

(source)

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over