11-68781872-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001876.4(CPT1A):c.1251T>C(p.Phe417=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,613,992 control chromosomes in the GnomAD database, including 710,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64534 hom., cov: 31)
  • Exomes 𝑓: 0.94 (646337 hom.)
• Consequence: CPT1A NM_001876.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.301

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 11-68781872-A-G is Benign according to our data. Variant chr11-68781872-A-G is described in ClinVar as [Benign]. Clinvar id is 166951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68781872-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.301 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPT1A	NM_001876.4	c.1251T>C	p.Phe417=	synonymous_variant	11/19	ENST00000265641.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT1A	ENST00000265641.10	c.1251T>C	p.Phe417=	synonymous_variant	11/19	1	NM_001876.4	P1
CPT1A	ENST00000376618.6	c.1251T>C	p.Phe417=	synonymous_variant	11/19	1
CPT1A	ENST00000540367.5	c.1251T>C	p.Phe417=	synonymous_variant	10/18	1
CPT1A	ENST00000539743.5	c.1251T>C	p.Phe417=	synonymous_variant	10/18	5		P1

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139810 AN: 152042 Hom.: 64499 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.977

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.921

GnomAD3 exomes AF: 0.933 AC: 234614 AN: 251492 Hom.: 109650 AF XY: 0.932 AC XY: 126642 AN XY: 135918

Gnomad AFR exome AF: 0.843

Gnomad AMR exome AF: 0.946

Gnomad ASJ exome AF: 0.952

Gnomad EAS exome AF: 0.909

Gnomad SAS exome AF: 0.886

Gnomad FIN exome AF: 0.972

Gnomad NFE exome AF: 0.949

Gnomad OTH exome AF: 0.937

GnomAD4 exome AF: 0.940 AC: 1374100 AN: 1461832 Hom.: 646337 Cov.: 51 AF XY: 0.939 AC XY: 682611 AN XY: 727228

Gnomad4 AFR exome AF: 0.845

Gnomad4 AMR exome AF: 0.944

Gnomad4 ASJ exome AF: 0.952

Gnomad4 EAS exome AF: 0.918

Gnomad4 SAS exome AF: 0.885

Gnomad4 FIN exome AF: 0.970

Gnomad4 NFE exome AF: 0.947

Gnomad4 OTH exome AF: 0.927

GnomAD4 genome AF: 0.919 AC: 139902 AN: 152160 Hom.: 64534 Cov.: 31 AF XY: 0.921 AC XY: 68500 AN XY: 74394

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.944

Gnomad4 ASJ AF: 0.949

Gnomad4 EAS AF: 0.910

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.977

Gnomad4 NFE AF: 0.949

Gnomad4 OTH AF: 0.922

Alfa AF: 0.937 Hom.: 46587

Bravo AF: 0.914

Asia WGS AF: 0.907 AC: 3152 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Carnitine palmitoyl transferase 1A deficiency Benign:3

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 16, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 15, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	0.83
Dann	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2228502; hg19: chr11-68549340;