rs3741054

Variant names:

• chr11-108121585-C-G
• rs3741054
• NM_000019.4:c.-22C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-108121585-C-G
• chr11-108121585-C-T
• chr11-108121585-C-A

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.-22C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,549,518 control chromosomes in the GnomAD database, including 22,130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1529 hom., cov: 34)
  • Exomes 𝑓: 0.17 (20601 hom.)
• Consequence: ACAT1 NM_000019.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.57
• Publications: 12 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=-0.83).
• BP6: Variant 11-108121585-C-G is Benign according to our data. Variant chr11-108121585-C-G is described in ClinVar as Benign. ClinVar VariationId is 302195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 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.-22C>G		5_prime_UTR	Exon 1 of 12	NP_000010.1	P24752-1
	ACAT1	NM_001386677.1		c.-22C>G		5_prime_UTR	Exon 1 of 12	NP_001373606.1	A0A5F9ZHL1
	ACAT1	NM_001386685.1		c.-386C>G		5_prime_UTR	Exon 1 of 13	NP_001373614.1	A0A5F9ZHJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAT1	ENST00000265838.9	TSL:1 MANE Select	c.-22C>G		5_prime_UTR	Exon 1 of 12	ENSP00000265838.4	P24752-1
	ACAT1	ENST00000299355.10	TSL:1	c.-22C>G		5_prime_UTR	Exon 1 of 6	ENSP00000299355.6	P24752-2
	ACAT1	ENST00000531813.5	TSL:1	n.-22C>G		non_coding_transcript_exon	Exon 1 of 8	ENSP00000435965.1	E9PRQ6

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20741 AN: 152196 Hom.: 1529 Cov.: 34

Gnomad AFR AF: 0.0951

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.131

GnomAD2 exomes AF: 0.142 AC: 21347 AN: 150434 AF XY: 0.147

Gnomad AFR exome AF: 0.0945

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.0191

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.141

GnomAD4 exome AF: 0.168 AC: 235381 AN: 1397204 Hom.: 20601 Cov.: 30 AF XY: 0.169 AC XY: 116234 AN XY: 689214

African (AFR) AF: 0.0967 AC: 3053 AN: 31572

American (AMR) AF: 0.109 AC: 3894 AN: 35708

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 3946 AN: 25150

East Asian (EAS) AF: 0.0432 AC: 1545 AN: 35730

South Asian (SAS) AF: 0.166 AC: 13124 AN: 79194

European-Finnish (FIN) AF: 0.164 AC: 7877 AN: 48030

Middle Eastern (MID) AF: 0.0950 AC: 527 AN: 5550

European-Non Finnish (NFE) AF: 0.179 AC: 192626 AN: 1078322

Other (OTH) AF: 0.152 AC: 8789 AN: 57948

GnomAD4 genome AF: 0.136 AC: 20738 AN: 152314 Hom.: 1529 Cov.: 34 AF XY: 0.134 AC XY: 10003 AN XY: 74472

African (AFR) AF: 0.0949 AC: 3943 AN: 41570

American (AMR) AF: 0.105 AC: 1607 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3472

East Asian (EAS) AF: 0.0238 AC: 123 AN: 5168

South Asian (SAS) AF: 0.154 AC: 742 AN: 4826

European-Finnish (FIN) AF: 0.154 AC: 1632 AN: 10618

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11725 AN: 68024

Other (OTH) AF: 0.129 AC: 274 AN: 2116

Alfa AF: 0.105 Hom.: 239

Bravo AF: 0.130

Asia WGS AF: 0.0890 AC: 312 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.40
DANN	Benign	0.45
PhyloP100		-1.6
PromoterAI		0.064	Neutral
Mutation Taster		=298/2	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: rs3741054; hg19: chr11-107992312; COSMIC: COSV54922494; COSMIC: COSV54922494;