11-68774781-CAAAAAAAAAA-CAAAAAAAA

Position:

• chr11-68774781-CAAAAAAAAAA-CAAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001876.4(CPT1A):​c.1575+533_1575+534del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000332 in 54,264 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: 𝑓 0.00033 (0 hom., cov: 28)
• Consequence: CPT1A NM_001876.4 intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.733

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-68774781-CAA-C is Pathogenic according to our data. Variant chr11-68774781-CAA-C is described in ClinVar as [Pathogenic]. Clinvar id is 9064.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1A	NM_001876.4	c.1575+533_1575+534del		intron_variant		ENST00000265641.10	NP_001867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000265641.10	c.1575+533_1575+534del		intron_variant		1	NM_001876.4	ENSP00000265641	P1
CPT1A	ENST00000376618.6	c.1575+533_1575+534del		intron_variant		1		ENSP00000365803
CPT1A	ENST00000540367.5	c.1575+533_1575+534del		intron_variant		1		ENSP00000439084
CPT1A	ENST00000539743.5	c.1575+533_1575+534del		intron_variant		5		ENSP00000446108	P1

Frequencies

GnomAD3 genomes AF: 0.000332 AC: 18 AN: 54240 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000449

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00357

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000190

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000332 AC: 18 AN: 54264 Hom.: 0 Cov.: 28 AF XY: 0.000353 AC XY: 9 AN XY: 25504

Gnomad4 AFR AF: 0.000204

Gnomad4 AMR AF: 0.000448

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00357

Gnomad4 NFE AF: 0.000190

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Carnitine palmitoyl transferase 1A deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2002

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs1169875761; hg19: chr11-68542249;