chr11-68774781-C-CA

Variant names:

• chr11-68774781-C-CA
• rs1169875761
• NM_001876.4:c.1575+534dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001876.4(CPT1A):​c.1575+534dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 53,528 control chromosomes in the GnomAD database, including 159 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (159 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1A	NM_001876.4	c.1575+534dupT		intron_variant	Intron 13 of 18	ENST00000265641.10	NP_001867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000265641.10	c.1575+534_1575+535insT		intron_variant	Intron 13 of 18	1	NM_001876.4	ENSP00000265641.4
CPT1A	ENST00000376618.6	c.1575+534_1575+535insT		intron_variant	Intron 13 of 18	1		ENSP00000365803.2
CPT1A	ENST00000540367.5	c.1575+534_1575+535insT		intron_variant	Intron 12 of 17	1		ENSP00000439084.1
CPT1A	ENST00000539743.5	c.1575+534_1575+535insT		intron_variant	Intron 12 of 17	5		ENSP00000446108.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 5549 AN: 53504 Hom.: 158 Cov.: 28

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0956

Gnomad OTH AF: 0.0973

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

GnomAD4 genome AF: 0.104 AC: 5554 AN: 53528 Hom.: 159 Cov.: 28 AF XY: 0.104 AC XY: 2619 AN XY: 25172

African (AFR) AF: 0.119 AC: 1726 AN: 14556

American (AMR) AF: 0.0652 AC: 289 AN: 4430

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 271 AN: 1554

East Asian (EAS) AF: 0.183 AC: 366 AN: 2004

South Asian (SAS) AF: 0.118 AC: 205 AN: 1730

European-Finnish (FIN) AF: 0.0419 AC: 94 AN: 2246

Middle Eastern (MID) AF: 0.115 AC: 12 AN: 104

European-Non Finnish (NFE) AF: 0.0957 AC: 2475 AN: 25872

Other (OTH) AF: 0.0980 AC: 67 AN: 684

Alfa AF: 0.0129 Hom.: 10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.73
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1169875761; hg19: chr11-68542249;