dbSNP rs1169875761: CPT1A:c.1575+525_1575+534delTTTTTTTTTT (chr11-68774781-CAAAAAAAAAA-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001876.4(CPT1A):c.1575+525_1575+534delTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000184 in 54,284 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., cov: 28)

Consequence

CPT1A
NM_001876.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

Publications

0 publications found

Variant links:

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

CPT1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CPT1A	NM_001876.4	MANE Select	c.1575+525_1575+534delTTTTTTTTTT	intron	N/A	NP_001867.2
CPT1A	NM_001440358.1		c.1575+525_1575+534delTTTTTTTTTT	intron	N/A	NP_001427287.1
CPT1A	NM_001440359.1		c.1575+525_1575+534delTTTTTTTTTT	intron	N/A	NP_001427288.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CPT1A	ENST00000265641.10	TSL:1 MANE Select	c.1575+525_1575+534delTTTTTTTTTT	intron	N/A	ENSP00000265641.4
CPT1A	ENST00000376618.6	TSL:1	c.1575+525_1575+534delTTTTTTTTTT	intron	N/A	ENSP00000365803.2
CPT1A	ENST00000540367.5	TSL:1	c.1575+525_1575+534delTTTTTTTTTT	intron	N/A	ENSP00000439084.1

Frequencies

GnomAD3 genomes

AF:

0.0000184

AC:

AN:

54284

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000568

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

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

GnomAD4 genome

AF:

0.0000184

AC:

AN:

54284

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

25498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

14674

American (AMR)

AF:

0.00

AC:

AN:

4452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1586

East Asian (EAS)

AF:

0.00

AC:

AN:

2020

South Asian (SAS)

AF:

0.000568

AC:

AN:

1760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

108

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

26378

Other (OTH)

AF:

0.00

AC:

AN:

690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over