11-68774781-C-CAA

Variant names:

• chr11-68774781-C-CAA
• rs1169875761
• NM_001876.4:c.1575+533_1575+534dupTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001876.4(CPT1A):​c.1575+533_1575+534dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 54,204 control chromosomes in the GnomAD database, including 8 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.011 (8 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0114 (620/54204) while in subpopulation AFR AF = 0.0386 (567/14674). AF 95% confidence interval is 0.036. There are 8 homozygotes in GnomAd4. There are 292 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1A	NM_001876.4	c.1575+533_1575+534dupTT		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+535insTT		intron_variant	Intron 13 of 18	1	NM_001876.4	ENSP00000265641.4
CPT1A	ENST00000376618.6	c.1575+534_1575+535insTT		intron_variant	Intron 13 of 18	1		ENSP00000365803.2
CPT1A	ENST00000540367.5	c.1575+534_1575+535insTT		intron_variant	Intron 12 of 17	1		ENSP00000439084.1
CPT1A	ENST00000539743.5	c.1575+534_1575+535insTT		intron_variant	Intron 12 of 17	5		ENSP00000446108.1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 616 AN: 54180 Hom.: 7 Cov.: 28

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00652

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000496

Gnomad SAS AF: 0.00114

Gnomad FIN AF: 0.00134

Gnomad MID AF: 0.00926

Gnomad NFE AF: 0.000418

Gnomad OTH AF: 0.00872

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

GnomAD4 genome AF: 0.0114 AC: 620 AN: 54204 Hom.: 8 Cov.: 28 AF XY: 0.0115 AC XY: 292 AN XY: 25478

African (AFR) AF: 0.0386 AC: 567 AN: 14674

American (AMR) AF: 0.00650 AC: 29 AN: 4462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1584

East Asian (EAS) AF: 0.000497 AC: 1 AN: 2012

South Asian (SAS) AF: 0.00115 AC: 2 AN: 1742

European-Finnish (FIN) AF: 0.00134 AC: 3 AN: 2246

Middle Eastern (MID) AF: 0.00943 AC: 1 AN: 106

European-Non Finnish (NFE) AF: 0.000418 AC: 11 AN: 26318

Other (OTH) AF: 0.00865 AC: 6 AN: 694

Alfa AF: 0.000266 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

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

Other links and lift over

dbSNP: rs1169875761; hg19: chr11-68542249;