rs1017639

chr11-68831066-A-C

Variant summary

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

The NM_001876.4(CPT1A):c.-14+10709T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 152,264 control chromosomes in the GnomAD database, including 465 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 0.065 (465 hom., cov: 33)
• Consequence: CPT1A NM_001876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPT1A	NM_001876.4	c.-14+10709T>G		intron_variant		ENST00000265641.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT1A	ENST00000265641.10	c.-14+10709T>G		intron_variant		1	NM_001876.4	P1
CPT1A	ENST00000376618.6	c.-14+10709T>G		intron_variant		1
CPT1A	ENST00000561996.1	c.-14+13079T>G		intron_variant		4
CPT1A	ENST00000569129.5	c.-14+8486T>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0643 AC: 9789 AN: 152146 Hom.: 462 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0672

Gnomad EAS AF: 0.0281

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0323

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0422

Gnomad OTH AF: 0.0521

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

GnomAD4 genome AF: 0.0645 AC: 9822 AN: 152264 Hom.: 465 Cov.: 33 AF XY: 0.0639 AC XY: 4755 AN XY: 74460

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0225

Gnomad4 ASJ AF: 0.0672

Gnomad4 EAS AF: 0.0280

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0323

Gnomad4 NFE AF: 0.0422

Gnomad4 OTH AF: 0.0525

Alfa AF: 0.0498 Hom.: 111

Bravo AF: 0.0635

Asia WGS AF: 0.102 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.10
Dann	Benign	0.29

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: rs1017639; hg19: chr11-68598534;