11-108121200-CAAAAAA-CAA

Variant names:

• chr11-108121200-CAAAA-C
• rs10561331
• NM_001386681.1:c.-199+4312_-199+4315delAAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001386681.1(ACAT1):​c.-199+4312_-199+4315delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 249,552 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000056 (0 hom., cov: 0)
  • Exomes 𝑓: 0.024 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0236 (2539/107452) while in subpopulation EAS AF= 0.0456 (167/3666). AF 95% confidence interval is 0.0399. There are 0 homozygotes in gnomad4_exome. There are 1405 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAT1	NM_001386681.1	c.-199+4312_-199+4315delAAAA		intron_variant	Intron 1 of 11		NP_001373610.1
ACAT1	NM_001386682.1	c.-416+4312_-416+4315delAAAA		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+4302delAAAA		intron_variant	Intron 1 of 11			ENSP00000500444.1
ENSG00000255467	ENST00000525548.1	n.389+92_389+95delTTTT		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0000563 AC: 8 AN: 142032 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000518

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000701

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000115

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000618

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0236 AC: 2539 AN: 107452 Hom.: 0 AF XY: 0.0244 AC XY: 1405 AN XY: 57524

Gnomad4 AFR exome AF: 0.0309

Gnomad4 AMR exome AF: 0.0248

Gnomad4 ASJ exome AF: 0.0237

Gnomad4 EAS exome AF: 0.0456

Gnomad4 SAS exome AF: 0.0263

Gnomad4 FIN exome AF: 0.0204

Gnomad4 NFE exome AF: 0.0217

Gnomad4 OTH exome AF: 0.0222

GnomAD4 genome AF: 0.0000563 AC: 8 AN: 142100 Hom.: 0 Cov.: 0 AF XY: 0.0000582 AC XY: 4 AN XY: 68684

Gnomad4 AFR AF: 0.0000517

Gnomad4 AMR AF: 0.0000700

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000115

Gnomad4 NFE AF: 0.0000618

Gnomad4 OTH AF: 0.00

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;