rs3019594

chr11-68838222-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001876.4(CPT1A):c.-14+3553G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 151,786 control chromosomes in the GnomAD database, including 51,275 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (51275 hom., cov: 28)
• Consequence: CPT1A NM_001876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPT1A	NM_001876.4	c.-14+3553G>A		intron_variant		ENST00000265641.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT1A	ENST00000265641.10	c.-14+3553G>A		intron_variant		1	NM_001876.4	P1
CPT1A	ENST00000376618.6	c.-14+3553G>A		intron_variant		1
CPT1A	ENST00000561996.1	c.-14+5923G>A		intron_variant		4
CPT1A	ENST00000569129.5	c.-14+1330G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.810 AC: 122806 AN: 151668 Hom.: 51254 Cov.: 28

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.946

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.919

Gnomad OTH AF: 0.824

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

GnomAD4 genome AF: 0.810 AC: 122879 AN: 151786 Hom.: 51275 Cov.: 28 AF XY: 0.809 AC XY: 59977 AN XY: 74160

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.919

Gnomad4 OTH AF: 0.820

Alfa AF: 0.900 Hom.: 80023

Bravo AF: 0.804

Asia WGS AF: 0.688 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.0
Dann	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs3019594; hg19: chr11-68605690;