rs140958507

Positions:

chr11-68794820-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001876.4(CPT1A):c.863G>A(p.Arg288Gln) variant causes a missense change. The variant allele was found at a frequency of 0.007 in 1,613,936 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0072 ( 53 hom. )

Consequence

CPT1A
NM_001876.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 4.58

Variant links:

Genes affected

CPT1A (HGNC:2328): (carnitine palmitoyltransferase 1A) The mitochondrial oxidation of long-chain fatty acids is initiated by the sequential action of carnitine palmitoyltransferase I (which is located in the outer membrane and is detergent-labile) and carnitine palmitoyltransferase II (which is located in the inner membrane and is detergent-stable), together with a carnitine-acylcarnitine translocase. CPT I is the key enzyme in the carnitine-dependent transport across the mitochondrial inner membrane and its deficiency results in a decreased rate of fatty acid beta-oxidation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CPT1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0125771165).

BP6

Variant 11-68794820-C-T is Benign according to our data. Variant chr11-68794820-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 203655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68794820-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00473 (720/152288) while in subpopulation NFE AF= 0.00826 (562/68036). AF 95% confidence interval is 0.00769. There are 2 homozygotes in gnomad4. There are 323 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1A	NM_001876.4 linkuse as main transcript	c.863G>A	p.Arg288Gln	missense_variant	8/19	ENST00000265641.10	NP_001867.2	P50416-1A0A024R5F4Q8WZ48B2RAQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000265641.10 linkuse as main transcript	c.863G>A	p.Arg288Gln	missense_variant	8/19	1	NM_001876.4	ENSP00000265641.4		P50416-1

Frequencies

GnomAD3 genomes

AF:

0.00473

AC:

720

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00538

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00826

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00530

AC:

1334

AN:

251488

Hom.:

AF XY:

0.00525

AC XY:

713

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000686

Gnomad FIN exome

AF:

0.00610

Gnomad NFE exome

AF:

0.00956

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00723

AC:

10570

AN:

1461648

Hom.:

Cov.:

AF XY:

0.00689

AC XY:

5010

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.000893

Gnomad4 FIN exome

AF:

0.00730

Gnomad4 NFE exome

AF:

0.00863

Gnomad4 OTH exome

AF:

0.00671

GnomAD4 genome

AF:

0.00473

AC:

720

AN:

152288

Hom.:

Cov.:

AF XY:

0.00434

AC XY:

323

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00538

Gnomad4 NFE

AF:

0.00826

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00685

Hom.:

Bravo

AF:

0.00427

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00815

AC:

ExAC

AF:

0.00586

AC:

711

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00725

EpiControl

AF:

0.00670

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Carnitine palmitoyl transferase 1A deficiency

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Dec 02, 2021	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 13, 2021	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	CPT1A: BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 03, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

CPT1A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 14, 2020

This variant is classified as 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

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.83

.;.;D;D;D

Eigen

Benign

0.17

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

.;D;.;D;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Uncertain

0.049

MutationAssessor

Uncertain

2.4

M;M;M;M;.

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.2

D;D;D;D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.028

D;D;D;D;D

Sift4G

Uncertain

0.027

D;D;D;D;D

Polyphen

0.81

P;P;B;B;.

Vest4

0.35

MVP

0.87

MPC

0.73

ClinPred

0.047

GERP RS

3.2

Varity_R

0.56

gMVP

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over