chr14-73537688-C-T

Variant names:

• chr14-73537688-C-T
• rs766196827
• NM_001037161.2:c.267C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037161.2. 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
	ACOT1	NM_001037161.2	MANE Select	c.267C>T	p.Pro89Pro	synonymous	Exon 1 of 3	NP_001032238.1	E9KL42
	HEATR4	NM_001220484.1	MANE Select	c.-151-7444G>A		intron	N/A	NP_001207413.1	Q86WZ0
	HEATR4	NM_203309.2		c.-72-14464G>A		intron	N/A	NP_976054.2	Q86WZ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOT1	ENST00000311148.9	TSL:1 MANE Select	c.267C>T	p.Pro89Pro	synonymous	Exon 1 of 3	ENSP00000311224.4	Q86TX2
	ACOT1	ENST00000557556.1	TSL:1	c.267C>T	p.Pro89Pro	synonymous	Exon 1 of 3	ENSP00000451764.1	G3V4F2
	HEATR4	ENST00000553558.6	TSL:2 MANE Select	c.-151-7444G>A		intron	N/A	ENSP00000450444.2	Q86WZ0

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

GnomAD2 exomes AF: 0.00703 AC: 1111 AN: 158060 AF XY: 0.00755

Gnomad AFR exome AF: 0.00138

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.000425

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0111

Gnomad NFE exome AF: 0.00976

Gnomad OTH exome AF: 0.00835

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000384 AC: 11 AN: 28658

American (AMR) AF: 0.00176 AC: 54 AN: 30604

Ashkenazi Jewish (ASJ) AF: 0.000152 AC: 3 AN: 19784

East Asian (EAS) AF: 0.00 AC: 0 AN: 11014

South Asian (SAS) AF: 0.00236 AC: 160 AN: 67902

European-Finnish (FIN) AF: 0.00377 AC: 125 AN: 33164

Middle Eastern (MID) AF: 0.00177 AC: 6 AN: 3388

European-Non Finnish (NFE) AF: 0.00131 AC: 1127 AN: 860624

Other (OTH) AF: 0.00156 AC: 70 AN: 44904

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000468 AC: 17 AN: 36316

American (AMR) AF: 0.000748 AC: 8 AN: 10698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2730

East Asian (EAS) AF: 0.00 AC: 0 AN: 1454

South Asian (SAS) AF: 0.00161 AC: 6 AN: 3730

European-Finnish (FIN) AF: 0.00296 AC: 20 AN: 6748

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 212

European-Non Finnish (NFE) AF: 0.00244 AC: 126 AN: 51636

Other (OTH) AF: 0.00127 AC: 2 AN: 1574

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00152 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.93
PhyloP100		-2.1
PromoterAI		0.015	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs766196827; hg19: chr14-74004392; COSMIC: COSV58574119; COSMIC: COSV58574119;