rs80356802

Positions:

• chr11-68775231-ACTACGGTTGGAAAATTCATCTGTAAGACTTCAAATGTGTTTCCCATCCCAGGTAAGTAACAATGGTTGGATAATCCGGACTTAC-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_001876.4(CPT1A):​c.1575+1_1575+84del variant causes a splice donor, splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CPT1A NM_001876.4 splice_donor, splice_donor_5th_base, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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 Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.049956933 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1A	NM_001876.4	c.1575+1_1575+84del		splice_donor_variant, splice_donor_5th_base_variant, intron_variant		ENST00000265641.10	NP_001867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000265641.10	c.1575+1_1575+84del		splice_donor_variant, splice_donor_5th_base_variant, intron_variant		1	NM_001876.4	ENSP00000265641	P1
CPT1A	ENST00000376618.6	c.1575+1_1575+84del		splice_donor_variant, splice_donor_5th_base_variant, intron_variant		1		ENSP00000365803
CPT1A	ENST00000540367.5	c.1575+1_1575+84del		splice_donor_variant, splice_donor_5th_base_variant, intron_variant		1		ENSP00000439084
CPT1A	ENST00000539743.5	c.1575+1_1575+84del		splice_donor_variant, splice_donor_5th_base_variant, intron_variant		5		ENSP00000446108	P1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs80356802; hg19: chr11-68542699;