rs613084

Variant names:

• chr11-68835689-C-A
• rs613084
• NM_001876.4:c.-14+6086G>T

Variant summary

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

The NM_001876.4(CPT1A):​c.-14+6086G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,082 control chromosomes in the GnomAD database, including 6,421 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 0.27 (6421 hom., cov: 32)
• Consequence: CPT1A NM_001876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662
• Publications: 24 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1A	NM_001876.4	MANE Select	c.-14+6086G>T		intron	N/A	NP_001867.2
	CPT1A	NM_001440358.1		c.-14+8456G>T		intron	N/A	NP_001427287.1
	CPT1A	NM_001440359.1		c.-14+3863G>T		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+6086G>T		intron	N/A	ENSP00000265641.4
	CPT1A	ENST00000376618.6	TSL:1	c.-14+6086G>T		intron	N/A	ENSP00000365803.2
	CPT1A	ENST00000569129.5	TSL:4	c.-14+3863G>T		intron	N/A	ENSP00000455116.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40394 AN: 151964 Hom.: 6425 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.266 AC: 40383 AN: 152082 Hom.: 6421 Cov.: 32 AF XY: 0.270 AC XY: 20046 AN XY: 74318

African (AFR) AF: 0.117 AC: 4870 AN: 41518

American (AMR) AF: 0.195 AC: 2976 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3468

East Asian (EAS) AF: 0.151 AC: 780 AN: 5164

South Asian (SAS) AF: 0.440 AC: 2118 AN: 4816

European-Finnish (FIN) AF: 0.425 AC: 4483 AN: 10554

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.338 AC: 22975 AN: 67962

Other (OTH) AF: 0.247 AC: 521 AN: 2110

Alfa AF: 0.319 Hom.: 15826

Bravo AF: 0.237

Asia WGS AF: 0.279 AC: 968 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
DANN	Benign	0.66
PhyloP100		-0.66
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: rs613084; hg19: chr11-68603157;