11-68774781-CAAAAAAAAAA-CAAAAAAAAAAAA

Position:

• chr11-68774781-CAAAAAAAAAA-CAAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001876.4(CPT1A):​c.1575+534_1575+535insTT 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

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 Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1A	NM_001876.4	c.1575+534_1575+535insTT		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+534_1575+535insTT		intron_variant		1	NM_001876.4	ENSP00000265641	P1
CPT1A	ENST00000376618.6	c.1575+534_1575+535insTT		intron_variant		1		ENSP00000365803
CPT1A	ENST00000540367.5	c.1575+534_1575+535insTT		intron_variant		1		ENSP00000439084
CPT1A	ENST00000539743.5	c.1575+534_1575+535insTT		intron_variant		5		ENSP00000446108	P1

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

Gnomad4 AFR AF: 0.0386

Gnomad4 AMR AF: 0.00650

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000497

Gnomad4 SAS AF: 0.00115

Gnomad4 FIN AF: 0.00134

Gnomad4 NFE AF: 0.000418

Gnomad4 OTH AF: 0.00865

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;