rs3741055

Variant names:

• chr11-108121598-T-A
• rs3741055
• NM_000019.4:c.-9T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-108121598-T-A
• chr11-108121598-T-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.-9T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,548,816 control chromosomes in the GnomAD database, including 83,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6932 hom., cov: 34)
  • Exomes 𝑓: 0.32 (76308 hom.)
• Consequence: ACAT1 NM_000019.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.31
• Publications: 14 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=-0.76).
• BP6: Variant 11-108121598-T-A is Benign according to our data. Variant chr11-108121598-T-A is described in ClinVar as Benign. ClinVar VariationId is 92294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.47 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.-9T>A		5_prime_UTR	Exon 1 of 12	NP_000010.1	P24752-1
	ACAT1	NM_001386677.1		c.-9T>A		5_prime_UTR	Exon 1 of 12	NP_001373606.1	A0A5F9ZHL1
	ACAT1	NM_001386685.1		c.-373T>A		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.-9T>A		5_prime_UTR	Exon 1 of 12	ENSP00000265838.4	P24752-1
	ACAT1	ENST00000299355.10	TSL:1	c.-9T>A		5_prime_UTR	Exon 1 of 6	ENSP00000299355.6	P24752-2
	ACAT1	ENST00000531813.5	TSL:1	n.-9T>A		non_coding_transcript_exon	Exon 1 of 8	ENSP00000435965.1	E9PRQ6

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41578 AN: 152116 Hom.: 6932 Cov.: 34

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.322

GnomAD2 exomes AF: 0.361 AC: 54490 AN: 150782 AF XY: 0.368

Gnomad AFR exome AF: 0.0814

Gnomad AMR exome AF: 0.470

Gnomad ASJ exome AF: 0.376

Gnomad EAS exome AF: 0.334

Gnomad FIN exome AF: 0.308

Gnomad NFE exome AF: 0.323

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.323 AC: 451699 AN: 1396582 Hom.: 76308 Cov.: 36 AF XY: 0.329 AC XY: 226982 AN XY: 688990

African (AFR) AF: 0.0827 AC: 2615 AN: 31628

American (AMR) AF: 0.461 AC: 16479 AN: 35752

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 9295 AN: 25150

East Asian (EAS) AF: 0.341 AC: 12199 AN: 35772

South Asian (SAS) AF: 0.481 AC: 38077 AN: 79204

European-Finnish (FIN) AF: 0.312 AC: 14977 AN: 47990

Middle Eastern (MID) AF: 0.454 AC: 2487 AN: 5472

European-Non Finnish (NFE) AF: 0.312 AC: 336497 AN: 1077710

Other (OTH) AF: 0.329 AC: 19073 AN: 57904

GnomAD4 genome AF: 0.273 AC: 41580 AN: 152234 Hom.: 6932 Cov.: 34 AF XY: 0.282 AC XY: 20959 AN XY: 74422

African (AFR) AF: 0.0926 AC: 3850 AN: 41576

American (AMR) AF: 0.398 AC: 6094 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1318 AN: 3460

East Asian (EAS) AF: 0.347 AC: 1783 AN: 5138

South Asian (SAS) AF: 0.486 AC: 2346 AN: 4828

European-Finnish (FIN) AF: 0.309 AC: 3280 AN: 10612

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21865 AN: 68004

Other (OTH) AF: 0.327 AC: 692 AN: 2116

Alfa AF: 0.314 Hom.: 2527

Bravo AF: 0.269

Asia WGS AF: 0.437 AC: 1517 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Deficiency of acetyl-CoA acetyltransferase (3)
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.0
DANN	Benign	0.71
PhyloP100		-1.3
PromoterAI		-0.013	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: rs3741055; hg19: chr11-107992325; COSMIC: COSV54920325; COSMIC: COSV54920325;