11-68794860-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001876.4(CPT1A):c.823G>A(p.Ala275Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 1,614,048 control chromosomes in the GnomAD database, including 4,186 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 387 hom., cov: 33)

Exomes 𝑓: 0.065 ( 3799 hom. )

Consequence

CPT1A
NM_001876.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: 0.806

Publications

43 publications found

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 Gene-Disease associations (from GenCC):

carnitine palmitoyl transferase 1A deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia

CPT1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025471747).

BP6

Variant 11-68794860-C-T is Benign according to our data. Variant chr11-68794860-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 65655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1A	NM_001876.4 link	c.823G>A	p.Ala275Thr	missense_variant	Exon 8 of 19	ENST00000265641.10	NP_001867.2	P50416-1A0A024R5F4Q8WZ48B2RAQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000265641.10 link	c.823G>A	p.Ala275Thr	missense_variant	Exon 8 of 19	1	NM_001876.4	ENSP00000265641.4		P50416-1

Frequencies

GnomAD3 genomes

AF:

0.0549

AC:

8354

AN:

152146

Hom.:

388

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.0507

Gnomad AMR

AF:

0.0278

Gnomad ASJ

AF:

0.0841

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0257

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0747

Gnomad OTH

AF:

0.0458

GnomAD2 exomes

AF:

0.0626

AC:

15741

AN:

251488

AF XY:

0.0636

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.0195

Gnomad ASJ exome

AF:

0.0815

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.0818

Gnomad OTH exome

AF:

0.0674

GnomAD4 exome

AF:

0.0655

AC:

95709

AN:

1461784

Hom.:

3799

Cov.:

AF XY:

0.0652

AC XY:

47388

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.00914

AC:

306

AN:

33476

American (AMR)

AF:

0.0201

AC:

901

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0820

AC:

2143

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.0270

AC:

2329

AN:

86254

European-Finnish (FIN)

AF:

0.164

AC:

8769

AN:

53410

Middle Eastern (MID)

AF:

0.0404

AC:

233

AN:

5768

European-Non Finnish (NFE)

AF:

0.0697

AC:

77544

AN:

1111928

Other (OTH)

AF:

0.0577

AC:

3482

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

4790

9580

14371

19161

23951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2654

5308

7962

10616

13270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0549

AC:

8356

AN:

152264

Hom.:

387

Cov.:

AF XY:

0.0573

AC XY:

4262

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0122

AC:

506

AN:

41568

American (AMR)

AF:

0.0277

AC:

423

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0841

AC:

292

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5194

South Asian (SAS)

AF:

0.0269

AC:

130

AN:

4830

European-Finnish (FIN)

AF:

0.166

AC:

1759

AN:

10574

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0747

AC:

5083

AN:

68026

Other (OTH)

AF:

0.0454

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

390

779

1169

1558

1948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0650

Hom.:

1346

Bravo

AF:

0.0425

TwinsUK

AF:

0.0696

AC:

258

ALSPAC

AF:

0.0641

AC:

247

ESP6500AA

AF:

0.0143

AC:

ESP6500EA

AF:

0.0770

AC:

661

ExAC

AF:

0.0647

AC:

7855

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Carnitine palmitoyl transferase 1A deficiency

Benign:6Other:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 03, 2015

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 05, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

Dec 24, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 10, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.37

CADD

Benign

5.0

(source)

DANN

Benign

0.95

DEOGEN2

Uncertain

0.48

.;.;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.84

.;T;.;T;T

MetaRNN

Benign

0.0025

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;N;N;N;.

PhyloP100

0.81

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.23

N;N;N;N;N

REVEL

Benign

0.27

Sift

Benign

0.43

T;T;T;T;T

Sift4G

Benign

0.24

T;T;T;T;T

Polyphen

0.0020

B;B;B;B;.

Vest4

0.069

MPC

0.40

ClinPred

0.0053

GERP RS

0.17

Varity_R

0.021

gMVP

0.57

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over