22-50570881-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_152246.3(CPT1B):c.2028+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,612,388 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00073 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (1 hom.)
• Consequence: CPT1B NM_152246.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.674

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 22-50570881-C-T is Benign according to our data. Variant chr22-50570881-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3050154.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPT1B	NM_152246.3	c.2028+10G>A		intron_variant		ENST00000312108.12
CHKB-CPT1B	NR_027928.2	n.3593+10G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT1B	ENST00000312108.12	c.2028+10G>A		intron_variant		1	NM_152246.3	P1

Frequencies

GnomAD3 genomes AF: 0.000729 AC: 111 AN: 152228 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000765 AC: 190 AN: 248306 Hom.: 1 AF XY: 0.000743 AC XY: 100 AN XY: 134544

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000721

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.00111 AC: 1615 AN: 1460042 Hom.: 1 Cov.: 32 AF XY: 0.00106 AC XY: 772 AN XY: 726242

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00289

Gnomad4 ASJ exome AF: 0.0000768

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00124

Gnomad4 OTH exome AF: 0.00136

GnomAD4 genome AF: 0.000729 AC: 111 AN: 152346 Hom.: 1 Cov.: 33 AF XY: 0.000604 AC XY: 45 AN XY: 74494

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000882

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000479 Hom.: 0

Bravo AF: 0.00108

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CPT1B-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 08, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.7
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs186124477; hg19: chr22-51009310;