chr14-73593804-C-A

Variant names:

• chr14-73593804-C-A
• rs35724886
• NM_152331.4:c.560C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152331.4(ACOT4):​c.560C>A​(p.Ala187Asp) variant causes a missense change. The variant allele was found at a frequency of 0.186 in 1,607,944 control chromosomes in the GnomAD database, including 32,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2210 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29806 hom.)
• Consequence: ACOT4 NM_152331.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.17
• Publications: 19 publications found

Genes affected

ACOT4 (HGNC:19748): (acyl-CoA thioesterase 4) Enables acyl-CoA hydrolase activity and succinyl-CoA hydrolase activity. Involved in carboxylic acid metabolic process; saturated monocarboxylic acid metabolic process; and succinyl-CoA metabolic process. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258603 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026230812).
• BP6: Variant 14-73593804-C-A is Benign according to our data. Variant chr14-73593804-C-A is described in ClinVar as Benign. ClinVar VariationId is 2798877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152331.4. 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
	ACOT4	NM_152331.4	MANE Select	c.560C>A	p.Ala187Asp	missense	Exon 2 of 3	NP_689544.3	Q8N9L9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOT4	ENST00000326303.5	TSL:1 MANE Select	c.560C>A	p.Ala187Asp	missense	Exon 2 of 3	ENSP00000323071.4	Q8N9L9
	ENSG00000258603	ENST00000664243.1		n.63-35832G>T		intron	N/A
	ENSG00000288797	ENST00000686335.1		n.279-1245C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22370 AN: 152052 Hom.: 2209 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.136

GnomAD2 exomes AF: 0.0495 AC: 10293 AN: 207986 AF XY: 0.0491

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.0153

Gnomad ASJ exome AF: 0.0319

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.142

Gnomad NFE exome AF: 0.0743

Gnomad OTH exome AF: 0.0452

GnomAD4 exome AF: 0.190 AC: 277149 AN: 1455774 Hom.: 29806 Cov.: 32 AF XY: 0.186 AC XY: 134915 AN XY: 723760

African (AFR) AF: 0.0453 AC: 1512 AN: 33360

American (AMR) AF: 0.0867 AC: 3836 AN: 44266

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2860 AN: 25964

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39700

South Asian (SAS) AF: 0.0723 AC: 6196 AN: 85754

European-Finnish (FIN) AF: 0.253 AC: 13450 AN: 53146

Middle Eastern (MID) AF: 0.0576 AC: 332 AN: 5762

European-Non Finnish (NFE) AF: 0.216 AC: 239115 AN: 1107676

Other (OTH) AF: 0.163 AC: 9828 AN: 60146

GnomAD4 genome AF: 0.147 AC: 22371 AN: 152170 Hom.: 2210 Cov.: 32 AF XY: 0.145 AC XY: 10827 AN XY: 74416

African (AFR) AF: 0.0523 AC: 2173 AN: 41562

American (AMR) AF: 0.107 AC: 1639 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3472

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5188

South Asian (SAS) AF: 0.0654 AC: 315 AN: 4814

European-Finnish (FIN) AF: 0.260 AC: 2743 AN: 10568

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14638 AN: 67970

Other (OTH) AF: 0.134 AC: 283 AN: 2114

Alfa AF: 0.0548 Hom.: 1425

Bravo AF: 0.133

ESP6500AA AF: 0.0172 AC: 76

ESP6500EA AF: 0.0974 AC: 837

ExAC AF: 0.128 AC: 15546

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		4.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.34
MPC		1.1
ClinPred		0.074	T
GERP RS		5.3
Varity_R		0.95
gMVP		0.95
Mutation Taster		=86/14	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: rs35724886; hg19: chr14-74060508; COSMIC: COSV108816711;