Variant rs2269383 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3BP4_StrongBA1

The NM_152246.3(CPT1B):c.959G>A(p.Gly320Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,612,678 control chromosomes in the GnomAD database, including 862 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.036 ( 207 hom., cov: 33)

Exomes 𝑓: 0.013 ( 655 hom. )

Consequence

CPT1B
NM_152246.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.86

Variant links:

Genes affected

CPT1B (HGNC:2329): (carnitine palmitoyltransferase 1B) The protein encoded by this gene, a member of the carnitine/choline acetyltransferase family, is the rate-controlling enzyme of the long-chain fatty acid beta-oxidation pathway in muscle mitochondria. This enzyme is required for the net transport of long-chain fatty acyl-CoAs from the cytoplasm into the mitochondria. Multiple transcript variants encoding different isoforms have been found for this gene, and read-through transcripts are expressed from the upstream locus that include exons from this gene. [provided by RefSeq, Jun 2009]

CPT1B links:

CHKB-CPT1B (HGNC:):

CHKB-CPT1B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 7: BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.0034022331).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1B	NM_152246.3 linkuse as main transcript	c.959G>A	p.Gly320Asp	missense_variant	9/20	ENST00000312108.12	NP_689452.1
CHKB-CPT1B	NR_027928.2 linkuse as main transcript	n.2529G>A		non_coding_transcript_exon_variant	19/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1B	ENST00000312108.12 linkuse as main transcript	c.959G>A	p.Gly320Asp	missense_variant	9/20	1	NM_152246.3	ENSP00000312189	P1	Q92523-1

Frequencies

GnomAD3 genomes

AF:

0.0361

AC:

5486

AN:

152130

Hom.:

207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0891

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0192

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.0310

Gnomad FIN

AF:

0.0193

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00494

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0264

AC:

6465

AN:

245092

Hom.:

308

AF XY:

0.0248

AC XY:

3297

AN XY:

132978

show subpopulations

Gnomad AFR exome

AF:

0.0896

Gnomad AMR exome

AF:

0.00918

Gnomad ASJ exome

AF:

0.00745

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.0279

Gnomad FIN exome

AF:

0.0158

Gnomad NFE exome

AF:

0.00536

Gnomad OTH exome

AF:

0.0176

GnomAD4 exome

AF:

0.0131

AC:

19085

AN:

1460430

Hom.:

655

Cov.:

AF XY:

0.0134

AC XY:

9735

AN XY:

726410

show subpopulations

Gnomad4 AFR exome

AF:

0.0933

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.00771

Gnomad4 EAS exome

AF:

0.142

Gnomad4 SAS exome

AF:

0.0277

Gnomad4 FIN exome

AF:

0.0147

Gnomad4 NFE exome

AF:

0.00473

Gnomad4 OTH exome

AF:

0.0191

GnomAD4 genome

AF:

0.0361

AC:

5500

AN:

152248

Hom.:

207

Cov.:

AF XY:

0.0382

AC XY:

2846

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0891

Gnomad4 AMR

AF:

0.0192

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.0313

Gnomad4 FIN

AF:

0.0193

Gnomad4 NFE

AF:

0.00494

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0388

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.0872

AC:

384

ESP6500EA

AF:

0.00616

AC:

ExAC

AF:

0.0271

AC:

3290

Asia WGS

AF:

0.0700

AC:

245

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Pathogenic

0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.89

D;D;D;D;.

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

.;.;.;D;D

MetaRNN

Benign

0.0034

T;T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Pathogenic

4.1

H;H;H;H;.

MutationTaster

Benign

2.0e-11

P;P;P;P;P;P;P

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.5

D;D;D;D;D

REVEL

Pathogenic

0.85

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Uncertain

0.011

D;D;D;D;D

Polyphen

1.0

D;D;D;D;.

Vest4

0.33

ClinPred

0.086

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.86

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over