rs3019594

Variant names:

• chr11-68838222-C-T
• rs3019594
• NM_001876.4:c.-14+3553G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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 -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 rank	MANE	Protein	UniProt
CPT1A	NM_001876.4	c.-14+3553G>A		intron_variant	Intron 1 of 18	ENST00000265641.10	NP_001867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000265641.10	c.-14+3553G>A		intron_variant	Intron 1 of 18	1	NM_001876.4	ENSP00000265641.4
CPT1A	ENST00000376618.6	c.-14+3553G>A		intron_variant	Intron 1 of 18	1		ENSP00000365803.2
CPT1A	ENST00000569129.5	c.-14+1330G>A		intron_variant	Intron 1 of 3	4		ENSP00000455116.1
CPT1A	ENST00000561996.1	c.-14+5923G>A		intron_variant	Intron 1 of 2	4		ENSP00000457663.1

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

African (AFR) AF: 0.617 AC: 25506 AN: 41326

American (AMR) AF: 0.882 AC: 13447 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3097 AN: 3472

East Asian (EAS) AF: 0.492 AC: 2529 AN: 5138

South Asian (SAS) AF: 0.866 AC: 4152 AN: 4792

European-Finnish (FIN) AF: 0.842 AC: 8884 AN: 10556

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.919 AC: 62422 AN: 67942

Other (OTH) AF: 0.820 AC: 1725 AN: 2104

Alfa AF: 0.891 Hom.: 99568

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
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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: rs3019594; hg19: chr11-68605690;