rs3741050

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000265838.9(ACAT1):c.436-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,614,120 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 8 hom. )

Consequence

ACAT1
ENST00000265838.9 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001337

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.353

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 11-108138894-G-A is Benign according to our data. Variant chr11-108138894-G-A is described in ClinVar as [Benign]. Clinvar id is 198028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00132 (201/152256) while in subpopulation EAS AF= 0.0135 (70/5184). AF 95% confidence interval is 0.011. There are 1 homozygotes in gnomad4. There are 108 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACAT1	NM_000019.4 linkuse as main transcript	c.436-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000265838.9	NP_000010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACAT1	ENST00000265838.9 linkuse as main transcript	c.436-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000019.4	ENSP00000265838	P1	P24752-1

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

201

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.0135

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00340

AC:

854

AN:

251438

Hom.:

AF XY:

0.00276

AC XY:

375

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.0124

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.00323

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00107

AC:

1567

AN:

1461864

Hom.:

Cov.:

AF XY:

0.000989

AC XY:

719

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.0124

Gnomad4 ASJ exome

AF:

0.000650

Gnomad4 EAS exome

AF:

0.0143

Gnomad4 SAS exome

AF:

0.000788

Gnomad4 FIN exome

AF:

0.00292

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.000960

GnomAD4 genome

AF:

0.00132

AC:

201

AN:

152256

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

108

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.0135

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000948

Hom.:

Bravo

AF:

0.00180

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of acetyl-CoA acetyltransferase

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 13, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.9

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000013

dbscSNV1_RF

Benign

0.0

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over