rs147563740

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_001876.4(CPT1A):c.2142+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000574 in 1,596,642 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 1 hom. )

Consequence

CPT1A
NM_001876.4 splice_region, intron

Scores

Splicing: ADA: 0.00002803

Clinical Significance

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

Conservation

PhyloP100: 0.672

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-68760217-G-A is Benign according to our data. Variant chr11-68760217-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 282930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000561 (811/1444414) while in subpopulation MID AF = 0.011 (49/4442). AF 95% confidence interval is 0.00857. There are 1 homozygotes in GnomAdExome4. There are 469 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1A	NM_001876.4 link	c.2142+8C>T		splice_region_variant, intron_variant	Intron 17 of 18	ENST00000265641.10	NP_001867.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CPT1A	ENST00000265641.10 link	c.2142+8C>T	splice_region_variant, intron_variant	Intron 17 of 18	1	NM_001876.4	ENSP00000265641.4
CPT1A	ENST00000376618.6 link	c.2142+8C>T	splice_region_variant, intron_variant	Intron 17 of 18	1		ENSP00000365803.2
CPT1A	ENST00000540367.5 link	c.2142+8C>T	splice_region_variant, intron_variant	Intron 16 of 17	1		ENSP00000439084.1
CPT1A	ENST00000539743.5 link	c.2142+8C>T	splice_region_variant, intron_variant	Intron 16 of 17	5		ENSP00000446108.1

Frequencies

GnomAD3 genomes

AF:

0.000684

AC:

104

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000799

AC:

187

AN:

233998

AF XY:

0.00101

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000243

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000909

Gnomad OTH exome

AF:

0.00274

GnomAD4 exome

AF:

0.000561

AC:

811

AN:

1444414

Hom.:

Cov.:

AF XY:

0.000653

AC XY:

469

AN XY:

717734

show subpopulations

African (AFR)

AF:

0.000663

AC:

AN:

33182

American (AMR)

AF:

0.000300

AC:

AN:

43346

Ashkenazi Jewish (ASJ)

AF:

0.000155

AC:

AN:

25808

East Asian (EAS)

AF:

0.0000761

AC:

AN:

39406

South Asian (SAS)

AF:

0.00205

AC:

173

AN:

84434

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52662

Middle Eastern (MID)

AF:

0.0110

AC:

AN:

4442

European-Non Finnish (NFE)

AF:

0.000429

AC:

473

AN:

1101516

Other (OTH)

AF:

0.00124

AC:

AN:

59618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000690

AC:

105

AN:

152228

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41552

American (AMR)

AF:

0.00118

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00270

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000882

AC:

AN:

67990

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000716

Hom.:

Bravo

AF:

0.000559

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CPT1A: BP4 -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Carnitine palmitoyl transferase 1A deficiency

Benign:2

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 06, 2019

Natera, Inc.

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

Aug 25, 2015

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 02, 2017

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.34

(source)

DANN

Benign

0.46

PhyloP100

0.67

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000028

dbscSNV1_RF

Benign

0.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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