rs613084

Positions:

• chr11-68835689-C-A

Variant summary

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

The NM_001876.4(CPT1A):​c.-14+6086G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,082 control chromosomes in the GnomAD database, including 6,421 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 0.27 (6421 hom., cov: 32)
• Consequence: CPT1A NM_001876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPT1A	NM_001876.4	c.-14+6086G>T		intron_variant		ENST00000265641.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT1A	ENST00000265641.10	c.-14+6086G>T		intron_variant		1	NM_001876.4	P1
CPT1A	ENST00000376618.6	c.-14+6086G>T		intron_variant		1
CPT1A	ENST00000561996.1	c.-14+8456G>T		intron_variant		4
CPT1A	ENST00000569129.5	c.-14+3863G>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40394 AN: 151964 Hom.: 6425 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.266 AC: 40383 AN: 152082 Hom.: 6421 Cov.: 32 AF XY: 0.270 AC XY: 20046 AN XY: 74318

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.247

Alfa AF: 0.326 Hom.: 11927

Bravo AF: 0.237

Asia WGS AF: 0.279 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
DANN	Benign	0.66

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: rs613084; hg19: chr11-68603157;