rs11228346

Positions:

• chr11-68774072-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001876.4(CPT1A):​c.1576-643T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 152,304 control chromosomes in the GnomAD database, including 604 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 0.080 (604 hom., cov: 31)
• Consequence: CPT1A NM_001876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPT1A	NM_001876.4	c.1576-643T>C		intron_variant		ENST00000265641.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT1A	ENST00000265641.10	c.1576-643T>C		intron_variant		1	NM_001876.4	P1
CPT1A	ENST00000376618.6	c.1576-643T>C		intron_variant		1
CPT1A	ENST00000540367.5	c.1576-643T>C		intron_variant		1
CPT1A	ENST00000539743.5	c.1576-643T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12216 AN: 152186 Hom.: 606 Cov.: 31

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.0916

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0304

Gnomad SAS AF: 0.0298

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0802 AC: 12216 AN: 152304 Hom.: 604 Cov.: 31 AF XY: 0.0786 AC XY: 5853 AN XY: 74470

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.0914

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0307

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.100

Alfa AF: 0.102 Hom.: 1101

Bravo AF: 0.0795

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs11228346; hg19: chr11-68541540;