rs75677837

Variant names:

• chr11-68793312-C-T
• rs75677837
• NM_001876.4:c.967+3G>A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BA1

The NM_001876.4(CPT1A):​c.967+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,607,360 control chromosomes in the GnomAD database, including 638 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (59 hom., cov: 31)
  • Exomes 𝑓: 0.020 (579 hom.)
• Consequence: CPT1A NM_001876.4 splice_region, intron
• Scores: Splicing: ADA: 0.004882
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.19

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BP6: Variant 11-68793312-C-T is Benign according to our data. Variant chr11-68793312-C-T is described in ClinVar as [Benign]. Clinvar id is 93978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68793312-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1A	NM_001876.4	c.967+3G>A		splice_region_variant, intron_variant	Intron 9 of 18	ENST00000265641.10	NP_001867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000265641.10	c.967+3G>A		splice_region_variant, intron_variant	Intron 9 of 18	1	NM_001876.4	ENSP00000265641.4

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2884 AN: 152172 Hom.: 59 Cov.: 31

Gnomad AFR AF: 0.00666

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0388

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0306

GnomAD3 exomes AF: 0.0326 AC: 8034 AN: 246402 Hom.: 242 AF XY: 0.0329 AC XY: 4377 AN XY: 133112

Gnomad AFR exome AF: 0.00609

Gnomad AMR exome AF: 0.0624

Gnomad ASJ exome AF: 0.0279

Gnomad EAS exome AF: 0.0764

Gnomad SAS exome AF: 0.0574

Gnomad FIN exome AF: 0.0185

Gnomad NFE exome AF: 0.0165

Gnomad OTH exome AF: 0.0328

GnomAD4 exome AF: 0.0197 AC: 28635 AN: 1455070 Hom.: 579 Cov.: 29 AF XY: 0.0209 AC XY: 15108 AN XY: 723630

Gnomad4 AFR exome AF: 0.00531

Gnomad4 AMR exome AF: 0.0610

Gnomad4 ASJ exome AF: 0.0274

Gnomad4 EAS exome AF: 0.0751

Gnomad4 SAS exome AF: 0.0596

Gnomad4 FIN exome AF: 0.0187

Gnomad4 NFE exome AF: 0.0127

Gnomad4 OTH exome AF: 0.0265

GnomAD4 genome AF: 0.0190 AC: 2886 AN: 152290 Hom.: 59 Cov.: 31 AF XY: 0.0199 AC XY: 1485 AN XY: 74466

Gnomad4 AFR AF: 0.00664

Gnomad4 AMR AF: 0.0388

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.0776

Gnomad4 SAS AF: 0.0621

Gnomad4 FIN AF: 0.0163

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0157 Hom.: 11

Bravo AF: 0.0208

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Carnitine palmitoyl transferase 1A deficiency Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 18, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Jan 15, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 17, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	18
DANN	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0049
dbscSNV1_RF	Benign	0.046
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: rs75677837; hg19: chr11-68560780;