11-68794860-C-T

Position:

chr11-68794860-C-T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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

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=0.0025471747).

BP6

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

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/exons	MANE	Protein	UniProt
CPT1A	NM_001876.4 linkuse as main transcript	c.823G>A	p.Ala275Thr	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.823G>A	p.Ala275Thr	missense_variant	8/19	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

GnomAD3 exomes

AF:

0.0626

AC:

15741

AN:

251488

Hom.:

771

AF XY:

0.0636

AC XY:

8642

AN XY:

135918

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 SAS exome

AF:

0.0249

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

Gnomad4 AFR exome

AF:

0.00914

Gnomad4 AMR exome

AF:

0.0201

Gnomad4 ASJ exome

AF:

0.0820

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0270

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.0697

Gnomad4 OTH exome

AF:

0.0577

GnomAD4 genome

AF:

0.0549

AC:

8356

AN:

152264

Hom.:

387

Cov.:

AF XY:

0.0573

AC XY:

4262

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0122

Gnomad4 AMR

AF:

0.0277

Gnomad4 ASJ

AF:

0.0841

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0269

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.0747

Gnomad4 OTH

AF:

0.0454

Alfa

AF:

0.0665

Hom.:

615

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

Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Aug 03, 2015	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 23, 2023	- -
not provided, no classification provided	literature only	GeneReviews	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 24, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 10, 2021	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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;.

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

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