rs1017639

Variant names:

• chr11-68831066-A-C
• rs1017639
• NM_001876.4:c.-14+10709T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001876.4(CPT1A):​c.-14+10709T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 152,264 control chromosomes in the GnomAD database, including 465 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 0.065 (465 hom., cov: 33)
• Consequence: CPT1A NM_001876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 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.-14+10709T>G		intron	N/A	NP_001867.2	P50416-1
	CPT1A	NM_001440358.1		c.-14+13079T>G		intron	N/A	NP_001427287.1
	CPT1A	NM_001440359.1		c.-14+8486T>G		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.-14+10709T>G		intron	N/A	ENSP00000265641.4	P50416-1
	CPT1A	ENST00000376618.6	TSL:1	c.-14+10709T>G		intron	N/A	ENSP00000365803.2	P50416-2
	CPT1A	ENST00000867662.1		c.-14+2743T>G		intron	N/A	ENSP00000537721.1

Frequencies

GnomAD3 genomes AF: 0.0643 AC: 9789 AN: 152146 Hom.: 462 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0672

Gnomad EAS AF: 0.0281

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0323

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0422

Gnomad OTH AF: 0.0521

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

GnomAD4 genome AF: 0.0645 AC: 9822 AN: 152264 Hom.: 465 Cov.: 33 AF XY: 0.0639 AC XY: 4755 AN XY: 74460

African (AFR) AF: 0.123 AC: 5097 AN: 41548

American (AMR) AF: 0.0225 AC: 344 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0672 AC: 233 AN: 3468

East Asian (EAS) AF: 0.0280 AC: 145 AN: 5182

South Asian (SAS) AF: 0.137 AC: 660 AN: 4820

European-Finnish (FIN) AF: 0.0323 AC: 343 AN: 10622

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0422 AC: 2868 AN: 68020

Other (OTH) AF: 0.0525 AC: 111 AN: 2114

Alfa AF: 0.0482 Hom.: 239

Bravo AF: 0.0635

Asia WGS AF: 0.102 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.29
PhyloP100		-0.73
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1017639;

hg19: chr11-68598534;