NM_001876.4:c.1575+528_1575+534dupTTTTTTT

Variant names:

• chr11-68774781-C-CAAAAAAA
• rs1169875761
• NM_001876.4:c.1575+528_1575+534dupTTTTTTT

Variant summary

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

The NM_001876.4(CPT1A):​c.1575+528_1575+534dupTTTTTTT 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 54,264 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 0.000018 (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, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

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+528_1575+534dupTTTTTTT		intron	N/A	NP_001867.2
	CPT1A	NM_001440358.1		c.1575+528_1575+534dupTTTTTTT		intron	N/A	NP_001427287.1
	CPT1A	NM_001440359.1		c.1575+528_1575+534dupTTTTTTT		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+535insTTTTTTT		intron	N/A	ENSP00000265641.4
	CPT1A	ENST00000376618.6	TSL:1	c.1575+534_1575+535insTTTTTTT		intron	N/A	ENSP00000365803.2
	CPT1A	ENST00000540367.5	TSL:1	c.1575+534_1575+535insTTTTTTT		intron	N/A	ENSP00000439084.1

Frequencies

GnomAD3 genomes AF: 0.0000184 AC: 1 AN: 54240 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: 0.000496

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

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: 54264 Hom.: 0 Cov.: 28 AF XY: 0.0000392 AC XY: 1 AN XY: 25500

African (AFR) AF: 0.00 AC: 0 AN: 14692

American (AMR) AF: 0.00 AC: 0 AN: 4460

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

East Asian (EAS) AF: 0.000498 AC: 1 AN: 2010

South Asian (SAS) AF: 0.00 AC: 0 AN: 1744

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 106

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 26356

Other (OTH) AF: 0.00 AC: 0 AN: 696

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;