11-108121200-CAAAAAA-CAAA

Variant names:

• chr11-108121200-CAAA-C
• rs10561331
• NM_001386681.1:c.-199+4313_-199+4315delAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001386681.1(ACAT1):​c.-199+4313_-199+4315delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 249,200 control chromosomes in the GnomAD database, including 21 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.010 (19 hom., cov: 0)
  • Exomes 𝑓: 0.20 (2 hom.)
• Consequence: ACAT1 NM_001386681.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702

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]

ENSG00000255467 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAT1	NM_001386681.1	c.-199+4313_-199+4315delAAA		intron_variant	Intron 1 of 11		NP_001373610.1
ACAT1	NM_001386682.1	c.-416+4313_-416+4315delAAA		intron_variant	Intron 1 of 12		NP_001373611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAT1	ENST00000672284.1	c.-199+4299_-199+4301delAAA		intron_variant	Intron 1 of 11			ENSP00000500444.1
ENSG00000255467	ENST00000525548.1	n.389+93_389+95delTTT		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1446 AN: 141968 Hom.: 19 Cov.: 0

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00617

Gnomad ASJ AF: 0.00240

Gnomad EAS AF: 0.00103

Gnomad SAS AF: 0.000885

Gnomad FIN AF: 0.00864

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00212

Gnomad OTH AF: 0.0104

GnomAD4 exome AF: 0.201 AC: 21494 AN: 107166 Hom.: 2 AF XY: 0.203 AC XY: 11649 AN XY: 57374

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.0102 AC: 1453 AN: 142034 Hom.: 19 Cov.: 0 AF XY: 0.0104 AC XY: 717 AN XY: 68656

Gnomad4 AFR AF: 0.0288

Gnomad4 AMR AF: 0.00616

Gnomad4 ASJ AF: 0.00240

Gnomad4 EAS AF: 0.00104

Gnomad4 SAS AF: 0.000888

Gnomad4 FIN AF: 0.00864

Gnomad4 NFE AF: 0.00212

Gnomad4 OTH AF: 0.0114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10561331; hg19: chr11-107991927;