rs1702003

chr1-54594689-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_147161.4(ACOT11):c.605G>A(p.Gly202Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0695 in 1,609,904 control chromosomes in the GnomAD database, including 13,105 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (4857 hom., cov: 33)
  • Exomes 𝑓: 0.059 (8248 hom.)
• Consequence: ACOT11 NM_147161.4 missense, splice_region
• Scores: Splicing: ADA: 0.000006643
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73

Genes affected

ACOT11 (HGNC:18156): (acyl-CoA thioesterase 11) This gene encodes a member of the acyl-CoA thioesterase family which catalyse the conversion of activated fatty acids to the corresponding non-esterified fatty acid and coenzyme A. Expression of a mouse homolog in brown adipose tissue is induced by low temperatures and repressed by warm temperatures. Higher levels of expression of the mouse homolog has been found in obesity-resistant mice compared with obesity-prone mice, suggesting a role of acyl-CoA thioesterase 11 in obesity. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012792647).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOT11	NM_147161.4	c.605G>A	p.Gly202Asp	missense_variant, splice_region_variant	6/16	ENST00000343744.7
ACOT11	NM_015547.4	c.605G>A	p.Gly202Asp	missense_variant, splice_region_variant	6/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOT11	ENST00000343744.7	c.605G>A	p.Gly202Asp	missense_variant, splice_region_variant	6/16	1	NM_147161.4	P1
ACOT11	ENST00000371316.3	c.605G>A	p.Gly202Asp	missense_variant, splice_region_variant	6/17	1
ACOT11	ENST00000481208.5	n.683G>A		splice_region_variant, non_coding_transcript_exon_variant	5/15	2
ACOT11	ENST00000498228.1	n.848G>A		splice_region_variant, non_coding_transcript_exon_variant	7/8	2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25806 AN: 152158 Hom.: 4838 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0400

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0375

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.131

GnomAD3 exomes AF: 0.112 AC: 27741 AN: 246820 Hom.: 3421 AF XY: 0.107 AC XY: 14231 AN XY: 133522

Gnomad AFR exome AF: 0.466

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.0510

Gnomad EAS exome AF: 0.199

Gnomad SAS exome AF: 0.205

Gnomad FIN exome AF: 0.0364

Gnomad NFE exome AF: 0.0298

Gnomad OTH exome AF: 0.0849

GnomAD4 exome AF: 0.0590 AC: 86040 AN: 1457628 Hom.: 8248 Cov.: 31 AF XY: 0.0620 AC XY: 44940 AN XY: 724486

Gnomad4 AFR exome AF: 0.474

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.0493

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.0369

Gnomad4 NFE exome AF: 0.0257

Gnomad4 OTH exome AF: 0.0847

GnomAD4 genome AF: 0.170 AC: 25873 AN: 152276 Hom.: 4857 Cov.: 33 AF XY: 0.169 AC XY: 12608 AN XY: 74446

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0400

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.0375

Gnomad4 NFE AF: 0.0302

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0692 Hom.: 1850

Bravo AF: 0.187

TwinsUK AF: 0.0262 AC: 97

ALSPAC AF: 0.0265 AC: 102

ESP6500AA AF: 0.448 AC: 1976

ESP6500EA AF: 0.0297 AC: 255

ExAC AF: 0.117 AC: 14222

Asia WGS AF: 0.226 AC: 785 AN: 3478

EpiCase AF: 0.0285

EpiControl AF: 0.0333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	13
Dann	Benign	0.19
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.12	T;T
MetaRNN	Benign	0.0013	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.7	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.78	N;N
REVEL	Benign	0.040
Sift	Benign	1.0	T;T
Sift4G	Benign	0.81	T;T
Polyphen		0.0	B;B
Vest4		0.079
MPC		0.25
ClinPred		0.0012	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000066
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

Other links and lift over

dbSNP: rs1702003; hg19: chr1-55060362; COSMIC: COSV59347443; COSMIC: COSV59347443;