11-68834506-C-G

Variant names:

• chr11-68834506-C-G
• rs597539
• NM_001876.4:c.-14+7269G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000265641.10(CPT1A):​c.-14+7269G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 151,966 control chromosomes in the GnomAD database, including 6,766 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 0.28 (6766 hom., cov: 32)
• Consequence: CPT1A ENST00000265641.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000265641.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1A	NM_001876.4	MANE Select	c.-14+7269G>C		intron	N/A	NP_001867.2
	CPT1A	NM_001440358.1		c.-14+9639G>C		intron	N/A	NP_001427287.1
	CPT1A	NM_001440359.1		c.-14+5046G>C		intron	N/A	NP_001427288.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1A	ENST00000265641.10	TSL:1 MANE Select	c.-14+7269G>C		intron	N/A	ENSP00000265641.4
	CPT1A	ENST00000376618.6	TSL:1	c.-14+7269G>C		intron	N/A	ENSP00000365803.2
	CPT1A	ENST00000569129.5	TSL:4	c.-14+5046G>C		intron	N/A	ENSP00000455116.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42677 AN: 151844 Hom.: 6767 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.281 AC: 42683 AN: 151966 Hom.: 6766 Cov.: 32 AF XY: 0.286 AC XY: 21232 AN XY: 74246

African (AFR) AF: 0.164 AC: 6816 AN: 41482

American (AMR) AF: 0.219 AC: 3346 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1396 AN: 3468

East Asian (EAS) AF: 0.196 AC: 1007 AN: 5144

South Asian (SAS) AF: 0.474 AC: 2282 AN: 4812

European-Finnish (FIN) AF: 0.423 AC: 4457 AN: 10528

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.332 AC: 22569 AN: 67954

Other (OTH) AF: 0.266 AC: 561 AN: 2108

Alfa AF: 0.309 Hom.: 967

Bravo AF: 0.256

Asia WGS AF: 0.317 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.4
DANN	Benign	0.69
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

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: rs597539; hg19: chr11-68601974;