chr11-68799242-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001876.4(CPT1A):c.669A>G(p.Leu223Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

CPT1A
NM_001876.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.39

Publications

0 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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 11-68799242-T-C is Benign according to our data. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-68799242-T-C is described in CliVar as Likely_benign. Clinvar id is 463968.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.39 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1A	NM_001876.4 link	c.669A>G	p.Leu223Leu	synonymous_variant	Exon 6 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.669A>G	p.Leu223Leu	synonymous_variant	Exon 6 of 19	1	NM_001876.4	ENSP00000265641.4		P50416-1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.0000477

AC:

AN:

251466

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.000687

AC:

AN:

33476

American (AMR)

AF:

0.0000671

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111886

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000171

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.000555

AC:

AN:

41452

American (AMR)

AF:

0.0000655

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68050

Other (OTH)

AF:

0.000955

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000328

Hom.:

Bravo

AF:

0.000181

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Carnitine palmitoyl transferase 1A deficiency

Benign:1

Jun 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CPT1A-related disorder

Benign:1

Jul 09, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.097

(source)

DANN

Benign

0.52

PhyloP100

-1.4

PromoterAI

0.036

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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