Variant chr11-68754748-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001031847.3(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
NM_001031847.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.914

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 65 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1A	NM_001031847.3 link	c.*68A>G		3_prime_UTR_variant	19/19		NP_001027017.1	P50416-2
CPT1A	XM_047426377.1 link	c.*68A>G		3_prime_UTR_variant	20/20		XP_047282333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1A	ENST00000376618 link	c.*68A>G		3_prime_UTR_variant	19/19	1		ENSP00000365803.2		P50416-2
CPT1A	ENST00000540367 link	c.*68A>G		3_prime_UTR_variant	18/18	1		ENSP00000439084.1		P50416-2

Frequencies

GnomAD3 genomes

AF:

0.0213

AC:

3242

AN:

152214

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.0291

AC XY:

9819

AN XY:

337214

show subpopulations

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.:

Cov.:

AF XY:

0.0198

AC XY:

1476

AN XY:

74496

show subpopulations

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.:

Bravo

AF:

0.0208

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over