7-87361398-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_021151.4(CROT):c.249G>T(p.Glu83Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000822 in 1,613,122 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00083 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00082 (23 hom.)
• Consequence: CROT NM_021151.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.539

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0104652345).
• BP6: Variant 7-87361398-G-T is Benign according to our data. Variant chr7-87361398-G-T is described in ClinVar as [Benign]. Clinvar id is 773213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000821 (1199/1460794) while in subpopulation AMR AF= 0.0258 (1144/44324). AF 95% confidence interval is 0.0246. There are 23 homozygotes in gnomad4_exome. There are 470 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CROT	NM_021151.4	c.249G>T	p.Glu83Asp	missense_variant	5/18	ENST00000331536.8
CROT	NM_001143935.2	c.333G>T	p.Glu111Asp	missense_variant	6/19
CROT	XM_011516337.4	c.249G>T	p.Glu83Asp	missense_variant	5/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CROT	ENST00000331536.8	c.249G>T	p.Glu83Asp	missense_variant	5/18	1	NM_021151.4	P1
CROT	ENST00000419147.6	c.333G>T	p.Glu111Asp	missense_variant	6/19	2
CROT	ENST00000442291.1	c.249G>T	p.Glu83Asp	missense_variant	4/17	5
CROT	ENST00000488850.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.000828 AC: 126 AN: 152210 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00397 AC: 995 AN: 250404 Hom.: 21 AF XY: 0.00274 AC XY: 371 AN XY: 135410

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0285

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00278

GnomAD4 exome AF: 0.000821 AC: 1199 AN: 1460794 Hom.: 23 Cov.: 31 AF XY: 0.000647 AC XY: 470 AN XY: 726724

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.0258

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.000414

GnomAD4 genome AF: 0.000834 AC: 127 AN: 152328 Hom.: 1 Cov.: 32 AF XY: 0.000873 AC XY: 65 AN XY: 74486

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00713

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000144 Hom.: 0

Bravo AF: 0.00185

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00292 AC: 355

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	8.3
Dann	Benign	0.94
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.81	T;T;T
MetaRNN	Benign	0.010	T;T;T
MetaSVM	Benign	-0.64	T
MutationTaster	Benign	0.67	N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.96	N;N;N
REVEL	Benign	0.29
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.44	T;T;T
Polyphen		0.0010	.;B;.
Vest4		0.15
MutPred		0.68		.;Loss of catalytic residue at W85 (P = 0.043);Loss of catalytic residue at W85 (P = 0.043);
MVP		0.26
MPC		0.027
ClinPred		0.0092	T
GERP RS		-5.6
Varity_R		0.15
gMVP		0.45

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: rs199970637; hg19: chr7-86990714;