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

Variant names:

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

Variant summary

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

The NM_001876.4(CPT1A):​c.-13-10303T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,884 control chromosomes in the GnomAD database, including 14,996 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 0.40 (14996 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1A	NM_001876.4	c.-13-10303T>C		intron_variant	Intron 1 of 18	ENST00000265641.10	NP_001867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000265641.10	c.-13-10303T>C		intron_variant	Intron 1 of 18	1	NM_001876.4	ENSP00000265641.4
CPT1A	ENST00000376618.6	c.-13-10303T>C		intron_variant	Intron 1 of 18	1		ENSP00000365803.2
CPT1A	ENST00000569129.5	c.-13-10303T>C		intron_variant	Intron 1 of 3	4		ENSP00000455116.1
CPT1A	ENST00000561996.1	c.-13-10303T>C		intron_variant	Intron 1 of 2	4		ENSP00000457663.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60606 AN: 151766 Hom.: 14997 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.399 AC: 60608 AN: 151884 Hom.: 14996 Cov.: 31 AF XY: 0.394 AC XY: 29206 AN XY: 74216

African (AFR) AF: 0.123 AC: 5113 AN: 41416

American (AMR) AF: 0.588 AC: 8978 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1453 AN: 3472

East Asian (EAS) AF: 0.278 AC: 1428 AN: 5142

South Asian (SAS) AF: 0.248 AC: 1194 AN: 4818

European-Finnish (FIN) AF: 0.383 AC: 4037 AN: 10538

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36610 AN: 67922

Other (OTH) AF: 0.450 AC: 950 AN: 2110

Alfa AF: 0.488 Hom.: 11061

Bravo AF: 0.410

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.56
PhyloP100		-0.22
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: rs11228368; hg19: chr11-68593258; COSMIC: COSV55762092;