chr11-108121592-C-G

Variant names:

• chr11-108121592-C-G
• rs113348145
• NM_000019.4:c.-15C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000019.4(ACAT1):​c.-15C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0038 in 1,550,244 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (106 hom., cov: 34)
  • Exomes 𝑓: 0.0020 (91 hom.)
• Consequence: ACAT1 NM_000019.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.04
• Publications: 1 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: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ENSG00000255467 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-108121592-C-G is Benign according to our data. Variant chr11-108121592-C-G is described in ClinVar as Benign. ClinVar VariationId is 166648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000019.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAT1	NM_000019.4	MANE Select	c.-15C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_000010.1	P24752-1
	ACAT1	NM_000019.4	MANE Select	c.-15C>G		5_prime_UTR	Exon 1 of 12	NP_000010.1	P24752-1
	ACAT1	NM_001386677.1		c.-15C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_001373606.1	A0A5F9ZHL1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAT1	ENST00000265838.9	TSL:1 MANE Select	c.-15C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000265838.4	P24752-1
	ACAT1	ENST00000299355.10	TSL:1	c.-15C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000299355.6	P24752-2
	ACAT1	ENST00000265838.9	TSL:1 MANE Select	c.-15C>G		5_prime_UTR	Exon 1 of 12	ENSP00000265838.4	P24752-1

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3101 AN: 152234 Hom.: 107 Cov.: 34

Gnomad AFR AF: 0.0706

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00870

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00955

GnomAD2 exomes AF: 0.00462 AC: 697 AN: 150906 AF XY: 0.00328

Gnomad AFR exome AF: 0.0714

Gnomad AMR exome AF: 0.00449

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.000924

GnomAD4 exome AF: 0.00199 AC: 2783 AN: 1397892 Hom.: 91 Cov.: 30 AF XY: 0.00167 AC XY: 1149 AN XY: 689580

African (AFR) AF: 0.0682 AC: 2155 AN: 31616

American (AMR) AF: 0.00515 AC: 184 AN: 35736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25156

East Asian (EAS) AF: 0.00 AC: 0 AN: 35774

South Asian (SAS) AF: 0.000278 AC: 22 AN: 79230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48104

Middle Eastern (MID) AF: 0.00596 AC: 33 AN: 5534

European-Non Finnish (NFE) AF: 0.0000945 AC: 102 AN: 1078796

Other (OTH) AF: 0.00495 AC: 287 AN: 57946

GnomAD4 genome AF: 0.0204 AC: 3102 AN: 152352 Hom.: 106 Cov.: 34 AF XY: 0.0193 AC XY: 1439 AN XY: 74498

African (AFR) AF: 0.0704 AC: 2928 AN: 41582

American (AMR) AF: 0.00869 AC: 133 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68046

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.0103 Hom.: 9

Bravo AF: 0.0227

Asia WGS AF: 0.00144 AC: 5 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Deficiency of acetyl-CoA acetyltransferase (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.57
PhyloP100		-2.0
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs113348145; hg19: chr11-107992319;