1-6385502-A-G

Position:

• chr1-6385502-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_181864.3(ACOT7):​c.165T>C​(p.Ile55Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,609,826 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00093 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (53 hom.)
• Consequence: ACOT7 NM_181864.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.690

Genes affected

ACOT7 (HGNC:24157): (acyl-CoA thioesterase 7) This gene encodes a member of the acyl coenzyme family. The encoded protein hydrolyzes the CoA thioester of palmitoyl-CoA and other long-chain fatty acids. Decreased expression of this gene may be associated with mesial temporal lobe epilepsy. Alternatively spliced transcript variants encoding distinct isoforms with different subcellular locations have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-6385502-A-G is Benign according to our data. Variant chr1-6385502-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3048654.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.69 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOT7	NM_007274.4	c.143+7755T>C		intron_variant		ENST00000361521.9	NP_009205.3
ACOT7	NM_181864.3	c.165T>C	p.Ile55Ile	synonymous_variant	1/9		NP_863654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOT7	ENST00000361521.9	c.143+7755T>C		intron_variant		1	NM_007274.4	ENSP00000354615.4

Frequencies

GnomAD3 genomes AF: 0.000935 AC: 142 AN: 151860 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000382

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000953 AC: 236 AN: 247514 Hom.: 5 AF XY: 0.00100 AC XY: 134 AN XY: 133918

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000975

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000191

Gnomad NFE exome AF: 0.00163

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00132 AC: 1919 AN: 1457848 Hom.: 53 Cov.: 31 AF XY: 0.00128 AC XY: 925 AN XY: 725142

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.00116

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000209

Gnomad4 NFE exome AF: 0.00159

Gnomad4 OTH exome AF: 0.00134

GnomAD4 genome AF: 0.000934 AC: 142 AN: 151978 Hom.: 3 Cov.: 32 AF XY: 0.000969 AC XY: 72 AN XY: 74266

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000382

Gnomad4 NFE AF: 0.00162

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00131 Hom.: 0

Bravo AF: 0.00111

EpiCase AF: 0.00207

EpiControl AF: 0.00261

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ACOT7-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.1
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs115915823; hg19: chr1-6445562;