11-68774781-CAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr11-68774781-C-CAAAAAAAAAAAAA
• rs1169875761
• NM_001876.4:c.1575+522_1575+534dupTTTTTTTTTTTTT

Variant summary

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

The NM_001876.4(CPT1A):​c.1575+522_1575+534dupTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000184 in 54,282 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000018 (0 hom., cov: 28)
• Consequence: CPT1A NM_001876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.733
• Publications: 0 publications found

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, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001876.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1A	NM_001876.4	MANE Select	c.1575+522_1575+534dupTTTTTTTTTTTTT		intron	N/A	NP_001867.2	P50416-1
	CPT1A	NM_001440358.1		c.1575+522_1575+534dupTTTTTTTTTTTTT		intron	N/A	NP_001427287.1
	CPT1A	NM_001440359.1		c.1575+522_1575+534dupTTTTTTTTTTTTT		intron	N/A	NP_001427288.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1A	ENST00000265641.10	TSL:1 MANE Select	c.1575+534_1575+535insTTTTTTTTTTTTT		intron	N/A	ENSP00000265641.4	P50416-1
	CPT1A	ENST00000376618.6	TSL:1	c.1575+534_1575+535insTTTTTTTTTTTTT		intron	N/A	ENSP00000365803.2	P50416-2
	CPT1A	ENST00000540367.5	TSL:1	c.1575+534_1575+535insTTTTTTTTTTTTT		intron	N/A	ENSP00000439084.1	P50416-2

Frequencies

GnomAD3 genomes AF: 0.0000184 AC: 1 AN: 54282 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000379

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000184 AC: 1 AN: 54282 Hom.: 0 Cov.: 28 AF XY: 0.0000392 AC XY: 1 AN XY: 25498

African (AFR) AF: 0.00 AC: 0 AN: 14674

American (AMR) AF: 0.00 AC: 0 AN: 4452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1586

East Asian (EAS) AF: 0.00 AC: 0 AN: 2020

South Asian (SAS) AF: 0.00 AC: 0 AN: 1758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 108

European-Non Finnish (NFE) AF: 0.0000379 AC: 1 AN: 26378

Other (OTH) AF: 0.00 AC: 0 AN: 690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.73

Splicing

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

Other links and lift over

dbSNP: rs1169875761; hg19: chr11-68542249;