11-108121200-CAA-C

Position:

• chr11-108121200-CAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000525548.1(ENSG00000255467):​n.389+94_389+95del variant causes a intron, non coding transcript 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: ENST00000525548.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.114

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAT1	NM_001386681.1	c.-199+4314_-199+4315del		intron_variant			NP_001373610.1
ACAT1	NM_001386682.1	c.-416+4314_-416+4315del		intron_variant			NP_001373611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000525548.1	n.389+94_389+95del		intron_variant, non_coding_transcript_variant		3
ACAT1	ENST00000672284.1	c.-199+4314_-199+4315del		intron_variant				ENSP00000500444

Frequencies

GnomAD3 genomes AF: 0.606 AC: 85962 AN: 141926 Hom.: 25508 Cov.: 0

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

Gnomad4 AFR exome AF: 0.386

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.406

Gnomad4 NFE exome AF: 0.401

Gnomad4 OTH exome AF: 0.414

GnomAD4 genome AF: 0.606 AC: 85983 AN: 141998 Hom.: 25501 Cov.: 0 AF XY: 0.610 AC XY: 41851 AN XY: 68654

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.884

Gnomad4 SAS AF: 0.736

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.624

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

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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;