Genetic Variant NM_001386681.1:c.-199+4314_-199+4315delAA (chr11-108121200-CAA-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001386681.1(ACAT1):c.-199+4314_-199+4315delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 251,168 control chromosomes in the GnomAD database, including 26,449 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.61 ( 25501 hom., cov: 0)

Exomes 𝑓: 0.41 ( 948 hom. )

Consequence

ACAT1
NM_001386681.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.114

Publications

0 publications found

Variant links:

Genes affected

ACAT1 (HGNC:93): (acetyl-CoA acetyltransferase 1) This gene encodes a mitochondrially localized enzyme that catalyzes the reversible formation of acetoacetyl-CoA from two molecules of acetyl-CoA. Defects in this gene are associated with 3-ketothiolase deficiency, an inborn error of isoleucine catabolism characterized by urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, and butanone. [provided by RefSeq, Feb 2009]

ACAT1 Gene-Disease associations (from GenCC):

beta-ketothiolase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACAT1 links:

ENSG00000255467 (HGNC:):

ENSG00000255467 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 11-108121200-CAA-C is Benign according to our data. Variant chr11-108121200-CAA-C is described in ClinVar as Benign. ClinVar VariationId is 1272094.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386681.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAT1	NM_001386681.1		c.-199+4314_-199+4315delAA		intron	N/A	NP_001373610.1	A0A5F9ZHJ0
	ACAT1	NM_001386682.1		c.-416+4314_-416+4315delAA		intron	N/A	NP_001373611.1	A0A5F9ZHJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAT1	ENST00000672284.1		c.-199+4299_-199+4300delAA		intron	N/A	ENSP00000500444.1	A0A5F9ZHJ0
	ENSG00000255467	ENST00000525548.1	TSL:3	n.389+94_389+95delTT		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.606

AC:

85962

AN:

141926

Hom.:

25508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.575

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.609

Gnomad EAS

AF:

0.885

Gnomad SAS

AF:

0.737

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.708

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.620

GnomAD4 exome

AF:

0.415

AC:

45271

AN:

109170

Hom.:

948

AF XY:

0.418

AC XY:

24490

AN XY:

58522

show subpopulations

African (AFR)

AF:

0.386

AC:

665

AN:

1724

American (AMR)

AF:

0.437

AC:

2058

AN:

4710

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

919

AN:

2240

East Asian (EAS)

AF:

0.492

AC:

1860

AN:

3782

South Asian (SAS)

AF:

0.443

AC:

9170

AN:

20700

European-Finnish (FIN)

AF:

0.406

AC:

2570

AN:

6332

Middle Eastern (MID)

AF:

0.406

AC:

147

AN:

362

European-Non Finnish (NFE)

AF:

0.401

AC:

25577

AN:

63750

Other (OTH)

AF:

0.414

AC:

2305

AN:

5570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1592

3185

4777

6370

7962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

218

436

654

872

1090

<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:

0.606

AC:

85983

AN:

141998

Hom.:

25501

Cov.:

AF XY:

0.610

AC XY:

41851

AN XY:

68654

show subpopulations

African (AFR)

AF:

0.575

AC:

22206

AN:

38640

American (AMR)

AF:

0.678

AC:

9685

AN:

14286

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

2031

AN:

3336

East Asian (EAS)

AF:

0.884

AC:

4276

AN:

4838

South Asian (SAS)

AF:

0.736

AC:

3312

AN:

4502

European-Finnish (FIN)

AF:

0.544

AC:

4736

AN:

8706

Middle Eastern (MID)

AF:

0.701

AC:

188

AN:

268

European-Non Finnish (NFE)

AF:

0.588

AC:

37982

AN:

64612

Other (OTH)

AF:

0.624

AC:

1217

AN:

1950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1597

3193

4790

6386

7983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.498

Hom.:

985

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.11

Splicing

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