ENST00000412227.6:c.*369G>A

Variant names:

• chr7-87359723-G-A
• rs802026
• ENST00000412227.6:c.*369G>A

Variant summary

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

The ENST00000412227.6(CROT):​c.*369G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,013,456 control chromosomes in the GnomAD database, including 7,477 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 0.14 (1975 hom., cov: 32)
  • Exomes 𝑓: 0.11 (5502 hom.)
• Consequence: CROT ENST00000412227.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.745
• Publications: 6 publications found

Genes affected

CROT (HGNC:2366): (carnitine O-octanoyltransferase) This gene encodes a member of the carnitine/choline acetyltransferase family. The encoded protein converts 4,8-dimethylnonanoyl-CoA to its corresponding carnitine ester. This transesterification occurs in the peroxisome and is necessary for transport of medium- and long- chain acyl-CoA molecules out of the peroxisome to the cytosol and mitochondria. The protein thus plays a role in lipid metabolism and fatty acid beta-oxidation. Alternatively spliced transcript variants have been described.[provided by RefSeq, Jan 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000412227.6. 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
	CROT	NM_021151.4	MANE Select	c.240+393G>A		intron	N/A	NP_066974.2
	CROT	NM_001243745.3		c.*369G>A		3_prime_UTR	Exon 4 of 4	NP_001230674.1	Q9UKG9-2
	CROT	NM_001143935.2		c.324+393G>A		intron	N/A	NP_001137407.1	Q9UKG9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CROT	ENST00000412227.6	TSL:1	c.*369G>A		3_prime_UTR	Exon 4 of 4	ENSP00000404867.2	Q9UKG9-2
	CROT	ENST00000331536.8	TSL:1 MANE Select	c.240+393G>A		intron	N/A	ENSP00000331981.4	Q9UKG9-1
	CROT	ENST00000419147.6	TSL:2	c.324+393G>A		intron	N/A	ENSP00000413575.2	Q9UKG9-3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22014 AN: 152042 Hom.: 1972 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0179

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.109 AC: 94063 AN: 861296 Hom.: 5502 Cov.: 23 AF XY: 0.110 AC XY: 43765 AN XY: 399110

African (AFR) AF: 0.257 AC: 4106 AN: 15994

American (AMR) AF: 0.108 AC: 185 AN: 1708

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 685 AN: 5714

East Asian (EAS) AF: 0.0199 AC: 88 AN: 4418

South Asian (SAS) AF: 0.150 AC: 2890 AN: 19222

European-Finnish (FIN) AF: 0.103 AC: 209 AN: 2036

Middle Eastern (MID) AF: 0.136 AC: 236 AN: 1730

European-Non Finnish (NFE) AF: 0.105 AC: 82330 AN: 781344

Other (OTH) AF: 0.114 AC: 3334 AN: 29130

GnomAD4 genome AF: 0.145 AC: 22056 AN: 152160 Hom.: 1975 Cov.: 32 AF XY: 0.144 AC XY: 10685 AN XY: 74382

African (AFR) AF: 0.248 AC: 10270 AN: 41486

American (AMR) AF: 0.102 AC: 1563 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3468

East Asian (EAS) AF: 0.0177 AC: 92 AN: 5188

South Asian (SAS) AF: 0.158 AC: 762 AN: 4826

European-Finnish (FIN) AF: 0.109 AC: 1150 AN: 10586

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7332 AN: 68010

Other (OTH) AF: 0.132 AC: 278 AN: 2114

Alfa AF: 0.116 Hom.: 4939

Bravo AF: 0.146

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.44
PhyloP100		0.74
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: rs802026;

hg19: chr7-86989039;