11-108121200-CAAAAAA-CAAAAAAA

Variant names:

• chr11-108121200-C-CA
• rs10561331
• NM_001386681.1:c.-199+4315dupA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001386681.1(ACAT1):​c.-199+4315dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00872 in 251,970 control chromosomes in the GnomAD database, including 9 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0093 (9 hom., cov: 0)
  • Exomes 𝑓: 0.0080 (0 hom.)
• Consequence: ACAT1 NM_001386681.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

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.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00929 (1320/142116) while in subpopulation NFE AF= 0.0154 (993/64678). AF 95% confidence interval is 0.0146. There are 9 homozygotes in gnomad4. There are 578 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAT1	NM_001386681.1	c.-199+4315dupA		intron_variant	Intron 1 of 11		NP_001373610.1
ACAT1	NM_001386682.1	c.-416+4315dupA		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+4298_-199+4299insA		intron_variant	Intron 1 of 11			ENSP00000500444.1
ENSG00000255467	ENST00000525548.1	n.389+95_389+96insT		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.00931 AC: 1322 AN: 142050 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.00267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00721

Gnomad ASJ AF: 0.0129

Gnomad EAS AF: 0.000412

Gnomad SAS AF: 0.00221

Gnomad FIN AF: 0.00574

Gnomad MID AF: 0.0103

Gnomad NFE AF: 0.0154

Gnomad OTH AF: 0.00729

GnomAD4 exome AF: 0.00799 AC: 878 AN: 109854 Hom.: 0 AF XY: 0.00759 AC XY: 447 AN XY: 58860

Gnomad4 AFR exome AF: 0.00634

Gnomad4 AMR exome AF: 0.00675

Gnomad4 ASJ exome AF: 0.0125

Gnomad4 EAS exome AF: 0.000792

Gnomad4 SAS exome AF: 0.00245

Gnomad4 FIN exome AF: 0.00440

Gnomad4 NFE exome AF: 0.0108

Gnomad4 OTH exome AF: 0.00552

GnomAD4 genome AF: 0.00929 AC: 1320 AN: 142116 Hom.: 9 Cov.: 0 AF XY: 0.00841 AC XY: 578 AN XY: 68694

Gnomad4 AFR AF: 0.00266

Gnomad4 AMR AF: 0.00721

Gnomad4 ASJ AF: 0.0129

Gnomad4 EAS AF: 0.000414

Gnomad4 SAS AF: 0.00200

Gnomad4 FIN AF: 0.00574

Gnomad4 NFE AF: 0.0154

Gnomad4 OTH AF: 0.00722

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;