rs2269383

chr22-50574346-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3 BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.86

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]

CHKB-CPT1B (HGNC:):

ACMG classification

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	UniProt
CPT1B	NM_152246.3	c.959G>A	p.Gly320Asp	missense_variant	9/20	ENST00000312108.12
CHKB-CPT1B	NR_027928.2	n.2529G>A		non_coding_transcript_exon_variant	19/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT1B	ENST00000312108.12	c.959G>A	p.Gly320Asp	missense_variant	9/20	1	NM_152246.3	P1

Frequencies

GnomAD3 genomes AF: 0.0361 AC: 5486 AN: 152130 Hom.: 207 Cov.: 33

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

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.: 32 AF XY: 0.0134 AC XY: 9735 AN XY: 726410

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.: 33 AF XY: 0.0382 AC XY: 2846 AN XY: 74460

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.: 63

Bravo AF: 0.0388

TwinsUK AF: 0.00405 AC: 15

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.0872 AC: 384

ESP6500EA AF: 0.00616 AC: 53

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	T
BayesDel_noAF	Pathogenic	0.32
Cadd	Pathogenic	28
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	D
MetaRNN	Benign	0.0034	T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	4.1	H;H;H;H;.
MutationTaster	Benign	2.0e-11	P;P;P;P;P;P;P
PrimateAI	Uncertain	0.71	T
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	T
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

Other links and lift over

dbSNP: rs2269383; hg19: chr22-51012775; COSMIC: COSV56417163; COSMIC: COSV56417163;