NM_001876.4:c.-13-10303T>A

Variant names:

• chr11-68825790-A-T
• rs11228368
• NM_001876.4:c.-13-10303T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001876.4(CPT1A):​c.-13-10303T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: CPT1A NM_001876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219
• Publications: 15 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001876.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1A	NM_001876.4	MANE Select	c.-13-10303T>A		intron	N/A	NP_001867.2
	CPT1A	NM_001440358.1		c.-13-10303T>A		intron	N/A	NP_001427287.1
	CPT1A	NM_001440359.1		c.-13-10303T>A		intron	N/A	NP_001427288.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1A	ENST00000265641.10	TSL:1 MANE Select	c.-13-10303T>A		intron	N/A	ENSP00000265641.4
	CPT1A	ENST00000376618.6	TSL:1	c.-13-10303T>A		intron	N/A	ENSP00000365803.2
	CPT1A	ENST00000867662.1		c.-14+8019T>A		intron	N/A	ENSP00000537721.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.8
DANN	Benign	0.56
PhyloP100		-0.22

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: rs11228368; hg19: chr11-68593258;