rs11228346

Variant names:

• chr11-68774072-A-G
• rs11228346
• NM_001876.4:c.1576-643T>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.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
• Publications: 5 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, Orphanet, Labcorp Genetics (formerly Invitae)

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 (NFE) allele frequency at 95% confidence interval = 0.102 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1A	NM_001876.4	MANE Select	c.1576-643T>C		intron	N/A	NP_001867.2	P50416-1
	CPT1A	NM_001440358.1		c.1576-643T>C		intron	N/A	NP_001427287.1
	CPT1A	NM_001440359.1		c.1576-643T>C		intron	N/A	NP_001427288.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1A	ENST00000265641.10	TSL:1 MANE Select	c.1576-643T>C		intron	N/A	ENSP00000265641.4	P50416-1
	CPT1A	ENST00000376618.6	TSL:1	c.1576-643T>C		intron	N/A	ENSP00000365803.2	P50416-2
	CPT1A	ENST00000540367.5	TSL:1	c.1576-643T>C		intron	N/A	ENSP00000439084.1	P50416-2

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

African (AFR) AF: 0.0265 AC: 1103 AN: 41588

American (AMR) AF: 0.0914 AC: 1398 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 658 AN: 3472

East Asian (EAS) AF: 0.0307 AC: 159 AN: 5186

South Asian (SAS) AF: 0.0294 AC: 142 AN: 4826

European-Finnish (FIN) AF: 0.112 AC: 1186 AN: 10604

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7090 AN: 68014

Other (OTH) AF: 0.100 AC: 212 AN: 2112

Alfa AF: 0.0992 Hom.: 1372

Bravo AF: 0.0795

Asia WGS AF: 0.0350 AC: 120 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	2.7
DANN	Benign	0.69
PhyloP100		0.30
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: rs11228346; hg19: chr11-68541540;