rs2924679

Positions:

• chr11-68789314-G-A

Variant summary

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

The NM_001876.4(CPT1A):​c.967+4001C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 152,206 control chromosomes in the GnomAD database, including 288 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 0.047 (288 hom., cov: 32)
• Consequence: CPT1A NM_001876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1A	NM_001876.4	c.967+4001C>T		intron_variant		ENST00000265641.10	NP_001867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000265641.10	c.967+4001C>T		intron_variant		1	NM_001876.4	ENSP00000265641	P1

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7150 AN: 152088 Hom.: 287 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0503

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.0826

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0149

Gnomad OTH AF: 0.0574

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

GnomAD4 genome AF: 0.0471 AC: 7168 AN: 152206 Hom.: 288 Cov.: 32 AF XY: 0.0476 AC XY: 3544 AN XY: 74422

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0503

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.0829

Gnomad4 SAS AF: 0.0737

Gnomad4 FIN AF: 0.0163

Gnomad4 NFE AF: 0.0149

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0363 Hom.: 76

Bravo AF: 0.0528

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.89

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: rs2924679; hg19: chr11-68556782;