5-81359147-T-G

Variant names:

• chr5-81359147-T-G
• rs4703516
• NM_130767.3:c.496+756A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130767.3(ACOT12):​c.496+756A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 152,144 control chromosomes in the GnomAD database, including 61,326 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.89 (61326 hom., cov: 31)
• Consequence: ACOT12 NM_130767.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929
• Publications: 7 publications found

Genes affected

ACOT12 (HGNC:24436): (acyl-CoA thioesterase 12) Enables identical protein binding activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid metabolic process. Predicted to act upstream of or within acetyl-CoA metabolic process. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130767.3. 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
	ACOT12	NM_130767.3	MANE Select	c.496+756A>C		intron	N/A	NP_570123.1	Q8WYK0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOT12	ENST00000307624.8	TSL:1 MANE Select	c.496+756A>C		intron	N/A	ENSP00000303246.3	Q8WYK0-1
	ACOT12	ENST00000905739.1		c.394+756A>C		intron	N/A	ENSP00000575798.1
	ACOT12	ENST00000905740.1		c.496+756A>C		intron	N/A	ENSP00000575799.1

Frequencies

GnomAD3 genomes AF: 0.893 AC: 135760 AN: 152026 Hom.: 61273 Cov.: 31

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.888

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.893 AC: 135863 AN: 152144 Hom.: 61326 Cov.: 31 AF XY: 0.887 AC XY: 65974 AN XY: 74380

African (AFR) AF: 0.976 AC: 40545 AN: 41538

American (AMR) AF: 0.819 AC: 12517 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.922 AC: 3200 AN: 3472

East Asian (EAS) AF: 0.501 AC: 2571 AN: 5132

South Asian (SAS) AF: 0.848 AC: 4092 AN: 4826

European-Finnish (FIN) AF: 0.858 AC: 9079 AN: 10576

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.897 AC: 60973 AN: 68000

Other (OTH) AF: 0.883 AC: 1864 AN: 2110

Alfa AF: 0.898 Hom.: 116554

Bravo AF: 0.891

Asia WGS AF: 0.701 AC: 2439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.70
DANN	Benign	0.74
PhyloP100		-0.93
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4703516;

hg19: chr5-80654966;