14-73537688-C-T

Position:

• chr14-73537688-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001037161.2(ACOT1):​c.267C>T​(p.Pro89Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 19)
  • Exomes 𝑓: 0.0014 (160 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACOT1 NM_001037161.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.09

Genes affected

ACOT1 (HGNC:33128): (acyl-CoA thioesterase 1) Enables acyl-CoA hydrolase activity. Involved in acyl-CoA metabolic process; long-chain fatty acid metabolic process; and very long-chain fatty acid metabolic process. Located in cytosol. [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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 14-73537688-C-T is Benign according to our data. Variant chr14-73537688-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 778485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.09 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOT1	NM_001037161.2	c.267C>T	p.Pro89Pro	synonymous_variant	1/3	ENST00000311148.9	NP_001032238.1
HEATR4	NM_001220484.1	c.-151-7444G>A		intron_variant		ENST00000553558.6	NP_001207413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOT1	ENST00000311148.9	c.267C>T	p.Pro89Pro	synonymous_variant	1/3	1	NM_001037161.2	ENSP00000311224.4
HEATR4	ENST00000553558.6	c.-151-7444G>A		intron_variant		2	NM_001220484.1	ENSP00000450444.2

Frequencies

GnomAD3 genomes AF: 0.00157 AC: 181 AN: 115642 Hom.: 1 Cov.: 19

Gnomad AFR AF: 0.000469

Gnomad AMI AF: 0.00331

Gnomad AMR AF: 0.000748

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00160

Gnomad FIN AF: 0.00296

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00244

Gnomad OTH AF: 0.00129

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00141 AC: 1556 AN: 1100042 Hom.: 160 Cov.: 29 AF XY: 0.00157 AC XY: 858 AN XY: 547842

Gnomad4 AFR exome AF: 0.000384

Gnomad4 AMR exome AF: 0.00176

Gnomad4 ASJ exome AF: 0.000152

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00236

Gnomad4 FIN exome AF: 0.00377

Gnomad4 NFE exome AF: 0.00131

Gnomad4 OTH exome AF: 0.00156

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00156 AC: 181 AN: 115702 Hom.: 1 Cov.: 19 AF XY: 0.00183 AC XY: 102 AN XY: 55750

Gnomad4 AFR AF: 0.000468

Gnomad4 AMR AF: 0.000748

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00161

Gnomad4 FIN AF: 0.00296

Gnomad4 NFE AF: 0.00244

Gnomad4 OTH AF: 0.00127

Alfa AF: 0.00152 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs766196827; hg19: chr14-74004392; COSMIC: COSV58574119; COSMIC: COSV58574119;