GeneBe

11-68774781-C-CAAAAAA

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001876.4(CPT1A):​c.1575+529_1575+534dupTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 54,056 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 28)

Consequence

CPT1A
NM_001876.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.733

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

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CPT1ANM_001876.4 linkc.1575+529_1575+534dupTTTTTT intron_variant Intron 13 of 18 ENST00000265641.10 NP_001867.2 P50416-1A0A024R5F4Q8WZ48B2RAQ8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CPT1AENST00000265641.10 linkc.1575+534_1575+535insTTTTTT intron_variant Intron 13 of 18 1 NM_001876.4 ENSP00000265641.4 P50416-1
CPT1AENST00000376618.6 linkc.1575+534_1575+535insTTTTTT intron_variant Intron 13 of 18 1 ENSP00000365803.2 P50416-2
CPT1AENST00000540367.5 linkc.1575+534_1575+535insTTTTTT intron_variant Intron 12 of 17 1 ENSP00000439084.1 P50416-2
CPT1AENST00000539743.5 linkc.1575+534_1575+535insTTTTTT intron_variant Intron 12 of 17 5 ENSP00000446108.1 P50416-1

Frequencies

GnomAD3 genomes
AF:
0.000204
AC:
11
AN:
54032
Hom.:
0
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.000205
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000450
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000445
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.000203
AC:
11
AN:
54056
Hom.:
0
Cov.:
28
AF XY:
0.000236
AC XY:
6
AN XY:
25410
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.000205
AC:
3
AN:
14648
American (AMR)
AF:
0.000449
AC:
2
AN:
4458
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
1580
East Asian (EAS)
AF:
0.00
AC:
0
AN:
2010
South Asian (SAS)
AF:
0.00
AC:
0
AN:
1742
European-Finnish (FIN)
AF:
0.000445
AC:
1
AN:
2248
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
106
European-Non Finnish (NFE)
AF:
0.000191
AC:
5
AN:
26214
Other (OTH)
AF:
0.00
AC:
0
AN:
686
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000617117), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
2
3
5
6
8
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00253
Hom.:
10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1169875761; hg19: chr11-68542249; API