22-50571288-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_152246.3(CPT1B):c.1745G>A(p.Arg582Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: CPT1B NM_152246.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.773

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07954657).
• BP6: Variant 22-50571288-C-T is Benign according to our data. Variant chr22-50571288-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2536943.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.1745G>A	p.Arg582Lys	missense_variant	15/20	ENST00000312108.12
CHKB-CPT1B	NR_027928.2	n.3311-1G>A		splice_acceptor_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT1B	ENST00000312108.12	c.1745G>A	p.Arg582Lys	missense_variant	15/20	1	NM_152246.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000161 AC: 4 AN: 248390 Hom.: 0 AF XY: 0.0000223 AC XY: 3 AN XY: 134520

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461514 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 727044

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	16
Dann	Benign	0.91
DEOGEN2	Benign	0.38	T;T;T;T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.46	N
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.080	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.77	N;N;N;N;.
MutationTaster	Benign	0.85	N;N;N;N;N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.36	N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.94	T;T;T;T;T
Sift4G	Benign	0.96	T;T;T;T;T
Polyphen		0.0	B;B;B;B;.
Vest4		0.086
MutPred		0.46		Loss of methylation at R580 (P = 0.0674);Loss of methylation at R580 (P = 0.0674);Loss of methylation at R580 (P = 0.0674);Loss of methylation at R580 (P = 0.0674);.;
MVP		0.74
ClinPred		0.042	T
GERP RS		0.81
Varity_R		0.063
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs764845864; hg19: chr22-51009717;