rs2924674

Variant names:

• chr11-68804309-G-A
• rs2924674
• NM_001876.4:c.454-208C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-68804309-G-A
• chr11-68804309-G-C
• chr11-68804309-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001876.4(CPT1A):​c.454-208C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.919 in 152,258 control chromosomes in the GnomAD database, including 64,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.92 (64913 hom., cov: 31)
• Consequence: CPT1A NM_001876.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-68804309-G-A is Benign according to our data. Variant chr11-68804309-G-A is described in ClinVar as [Benign]. Clinvar id is 678470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1A	NM_001876.4	c.454-208C>T		intron_variant	Intron 4 of 18	ENST00000265641.10	NP_001867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000265641.10	c.454-208C>T		intron_variant	Intron 4 of 18	1	NM_001876.4	ENSP00000265641.4
CPT1A	ENST00000376618.6	c.454-208C>T		intron_variant	Intron 4 of 18	1		ENSP00000365803.2
CPT1A	ENST00000540367.5	c.454-208C>T		intron_variant	Intron 3 of 17	1		ENSP00000439084.1
CPT1A	ENST00000539743.5	c.454-208C>T		intron_variant	Intron 3 of 17	5		ENSP00000446108.1

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139926 AN: 152140 Hom.: 64893 Cov.: 31

Gnomad AFR AF: 0.784

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.933

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.984

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.919 AC: 139993 AN: 152258 Hom.: 64913 Cov.: 31 AF XY: 0.920 AC XY: 68495 AN XY: 74442

African (AFR) AF: 0.784 AC: 32545 AN: 41516

American (AMR) AF: 0.933 AC: 14258 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 3368 AN: 3470

East Asian (EAS) AF: 0.935 AC: 4844 AN: 5182

South Asian (SAS) AF: 0.926 AC: 4471 AN: 4826

European-Finnish (FIN) AF: 0.983 AC: 10441 AN: 10618

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.984 AC: 66954 AN: 68038

Other (OTH) AF: 0.916 AC: 1936 AN: 2114

Alfa AF: 0.964 Hom.: 114619

Bravo AF: 0.911

Asia WGS AF: 0.919 AC: 3199 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.67
PhyloP100		-1.1
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: rs2924674; hg19: chr11-68571777;