Genetic Variant ACAA1:c.171+66A>C (chr3-38136799-T-G) – 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.171+66A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,485,338 control chromosomes in the GnomAD database, including 1,731 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 0.057 ( 274 hom., cov: 33)

Exomes 𝑓: 0.044 ( 1457 hom. )

Consequence

ACAA1
NM_001607.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.286

Publications

16 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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0838 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.171+66A>C	intron	N/A	NP_001598.1
ACAA1	NM_001130410.2		c.171+66A>C	intron	N/A	NP_001123882.1
ACAA1	NR_024024.2		n.263+66A>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ACAA1	ENST00000333167.13	TSL:1 MANE Select	c.171+66A>C	intron	N/A	ENSP00000333664.8
ACAA1	ENST00000301810.11	TSL:1	c.171+66A>C	intron	N/A	ENSP00000301810.7
ACAA1	ENST00000411549.5	TSL:1	n.171+66A>C	intron	N/A	ENSP00000414021.1

Frequencies

GnomAD3 genomes

AF:

0.0573

AC:

8703

AN:

151952

Hom.:

274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0860

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0436

Gnomad ASJ

AF:

0.0424

Gnomad EAS

AF:

0.0108

Gnomad SAS

AF:

0.0155

Gnomad FIN

AF:

0.0816

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0467

Gnomad OTH

AF:

0.0565

GnomAD4 exome

AF:

0.0443

AC:

59112

AN:

1333270

Hom.:

1457

Cov.:

AF XY:

0.0436

AC XY:

28498

AN XY:

654216

show subpopulations

African (AFR)

AF:

0.0890

AC:

2516

AN:

28258

American (AMR)

AF:

0.0343

AC:

839

AN:

24486

Ashkenazi Jewish (ASJ)

AF:

0.0379

AC:

770

AN:

20308

East Asian (EAS)

AF:

0.00422

AC:

144

AN:

34120

South Asian (SAS)

AF:

0.0188

AC:

1294

AN:

69006

European-Finnish (FIN)

AF:

0.0726

AC:

3136

AN:

43200

Middle Eastern (MID)

AF:

0.0848

AC:

342

AN:

4034

European-Non Finnish (NFE)

AF:

0.0451

AC:

47579

AN:

1054606

Other (OTH)

AF:

0.0451

AC:

2492

AN:

55252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

3319

6638

9957

13276

16595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1822

3644

5466

7288

9110

<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:

0.0573

AC:

8714

AN:

152068

Hom.:

274

Cov.:

AF XY:

0.0580

AC XY:

4316

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0861

AC:

3574

AN:

41502

American (AMR)

AF:

0.0435

AC:

665

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0424

AC:

147

AN:

3466

East Asian (EAS)

AF:

0.0109

AC:

AN:

5150

South Asian (SAS)

AF:

0.0155

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0816

AC:

862

AN:

10564

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0467

AC:

3173

AN:

67956

Other (OTH)

AF:

0.0564

AC:

119

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

429

857

1286

1714

2143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0466

Hom.:

244

Bravo

AF:

0.0559

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.6

(source)

DANN

Benign

0.56

PhyloP100

-0.29

PromoterAI

-0.032

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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