11-68781872-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001876.4(CPT1A):c.1251T>C(p.Phe417Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,613,992 control chromosomes in the GnomAD database, including 710,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 64534 hom., cov: 31)

Exomes 𝑓: 0.94 ( 646337 hom. )

Consequence

CPT1A
NM_001876.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.301

Publications

24 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 11-68781872-A-G is Benign according to our data. Variant chr11-68781872-A-G is described in ClinVar as Benign. ClinVar VariationId is 166951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.301 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1A	NM_001876.4 link	c.1251T>C	p.Phe417Phe	synonymous_variant	Exon 11 of 19	ENST00000265641.10	NP_001867.2	P50416-1A0A024R5F4Q8WZ48B2RAQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CPT1A	ENST00000265641.10 link	c.1251T>C	p.Phe417Phe	synonymous_variant	Exon 11 of 19	1	NM_001876.4	ENSP00000265641.4	P50416-1
CPT1A	ENST00000376618.6 link	c.1251T>C	p.Phe417Phe	synonymous_variant	Exon 11 of 19	1		ENSP00000365803.2	P50416-2
CPT1A	ENST00000540367.5 link	c.1251T>C	p.Phe417Phe	synonymous_variant	Exon 10 of 18	1		ENSP00000439084.1	P50416-2
CPT1A	ENST00000539743.5 link	c.1251T>C	p.Phe417Phe	synonymous_variant	Exon 10 of 18	5		ENSP00000446108.1	P50416-1

Frequencies

GnomAD3 genomes

AF:

0.920

AC:

139810

AN:

152042

Hom.:

64499

Cov.:

show subpopulations

Gnomad AFR

AF:

0.849

Gnomad AMI

AF:

0.975

Gnomad AMR

AF:

0.944

Gnomad ASJ

AF:

0.949

Gnomad EAS

AF:

0.910

Gnomad SAS

AF:

0.890

Gnomad FIN

AF:

0.977

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.949

Gnomad OTH

AF:

0.921

GnomAD2 exomes

AF:

0.933

AC:

234614

AN:

251492

AF XY:

0.932

show subpopulations

Gnomad AFR exome

AF:

0.843

Gnomad AMR exome

AF:

0.946

Gnomad ASJ exome

AF:

0.952

Gnomad EAS exome

AF:

0.909

Gnomad FIN exome

AF:

0.972

Gnomad NFE exome

AF:

0.949

Gnomad OTH exome

AF:

0.937

GnomAD4 exome

AF:

0.940

AC:

1374100

AN:

1461832

Hom.:

646337

Cov.:

AF XY:

0.939

AC XY:

682611

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.845

AC:

28277

AN:

33480

American (AMR)

AF:

0.944

AC:

42209

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.952

AC:

24891

AN:

26136

East Asian (EAS)

AF:

0.918

AC:

36440

AN:

39700

South Asian (SAS)

AF:

0.885

AC:

76357

AN:

86258

European-Finnish (FIN)

AF:

0.970

AC:

51815

AN:

53418

Middle Eastern (MID)

AF:

0.880

AC:

5073

AN:

5766

European-Non Finnish (NFE)

AF:

0.947

AC:

1053034

AN:

1111956

Other (OTH)

AF:

0.927

AC:

56004

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

4582

9164

13745

18327

22909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21594

43188

64782

86376

107970

<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:

0.919

AC:

139902

AN:

152160

Hom.:

64534

Cov.:

AF XY:

0.921

AC XY:

68500

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.849

AC:

35218

AN:

41488

American (AMR)

AF:

0.944

AC:

14419

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.949

AC:

3294

AN:

3472

East Asian (EAS)

AF:

0.910

AC:

4690

AN:

5154

South Asian (SAS)

AF:

0.890

AC:

4290

AN:

4822

European-Finnish (FIN)

AF:

0.977

AC:

10355

AN:

10600

Middle Eastern (MID)

AF:

0.854

AC:

251

AN:

294

European-Non Finnish (NFE)

AF:

0.949

AC:

64549

AN:

68024

Other (OTH)

AF:

0.922

AC:

1947

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

566

1131

1697

2262

2828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<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:

0.929

Hom.:

57133

Bravo

AF:

0.914

Asia WGS

AF:

0.907

AC:

3152

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Carnitine palmitoyl transferase 1A deficiency

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 16, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 15, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.83

(source)

DANN

Benign

0.37

PhyloP100

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

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