11-68754748-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000376618.6(CPT1A):c.*68A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 773,532 control chromosomes in the GnomAD database, including 371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (65 hom., cov: 32)
  • Exomes 𝑓: 0.027 (306 hom.)
• Consequence: CPT1A ENST00000376618.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.914

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-68754748-T-C is Benign according to our data. Variant chr11-68754748-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1218063.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0213 (3245/152332) while in subpopulation SAS AF= 0.0373 (180/4828). AF 95% confidence interval is 0.0333. There are 65 homozygotes in gnomad4. There are 1476 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 65 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPT1A	NM_001031847.3	c.*68A>G		3_prime_UTR_variant	19/19
CPT1A	XM_047426377.1	c.*68A>G		3_prime_UTR_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT1A	ENST00000376618.6	c.*68A>G		3_prime_UTR_variant	19/19	1
CPT1A	ENST00000540367.5	c.*68A>G		3_prime_UTR_variant	18/18	1

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3242 AN: 152214 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.00647

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.00744

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0345

Gnomad OTH AF: 0.0211

GnomAD4 exome AF: 0.0273 AC: 16969 AN: 621200 Hom.: 306 Cov.: 0 AF XY: 0.0291 AC XY: 9819 AN XY: 337214

Gnomad4 AFR exome AF: 0.00545

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.0177

Gnomad4 EAS exome AF: 0.0000279

Gnomad4 SAS exome AF: 0.0414

Gnomad4 FIN exome AF: 0.00973

Gnomad4 NFE exome AF: 0.0338

Gnomad4 OTH exome AF: 0.0263

GnomAD4 genome AF: 0.0213 AC: 3245 AN: 152332 Hom.: 65 Cov.: 32 AF XY: 0.0198 AC XY: 1476 AN XY: 74496

Gnomad4 AFR AF: 0.00645

Gnomad4 AMR AF: 0.0145

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0373

Gnomad4 FIN AF: 0.00744

Gnomad4 NFE AF: 0.0345

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0262 Hom.: 11

Bravo AF: 0.0208

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.061
Dann	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs75022915; hg19: chr11-68522216; COSMIC: COSV54832654; COSMIC: COSV54832654;