chr11-108126738-T-A

Variant names:

• chr11-108126738-T-A
• rs11212515
• NM_000019.4:c.72+5060T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000019.4(ACAT1):​c.72+5060T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 150,600 control chromosomes in the GnomAD database, including 6,840 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6840 hom., cov: 29)
• Consequence: ACAT1 NM_000019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402
• Publications: 4 publications found

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: ClinGen, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACAT1	NM_000019.4	c.72+5060T>A		intron_variant	Intron 1 of 11	ENST00000265838.9	NP_000010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACAT1	ENST00000265838.9	c.72+5060T>A		intron_variant	Intron 1 of 11	1	NM_000019.4	ENSP00000265838.4

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41043 AN: 150496 Hom.: 6840 Cov.: 29

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.325

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.273 AC: 41043 AN: 150600 Hom.: 6840 Cov.: 29 AF XY: 0.280 AC XY: 20577 AN XY: 73412

African (AFR) AF: 0.0926 AC: 3813 AN: 41170

American (AMR) AF: 0.397 AC: 5948 AN: 14978

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1340 AN: 3466

East Asian (EAS) AF: 0.329 AC: 1668 AN: 5070

South Asian (SAS) AF: 0.491 AC: 2337 AN: 4764

European-Finnish (FIN) AF: 0.303 AC: 3045 AN: 10058

Middle Eastern (MID) AF: 0.538 AC: 156 AN: 290

European-Non Finnish (NFE) AF: 0.322 AC: 21854 AN: 67818

Other (OTH) AF: 0.330 AC: 685 AN: 2078

Alfa AF: 0.286 Hom.: 869

Bravo AF: 0.269

Asia WGS AF: 0.434 AC: 1507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.67
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11212515; hg19: chr11-107997465;