rs3213445

Positions:

• chr22-50577409-T-A
• chr22-50577409-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152246.3(CPT1B):​c.196A>T​(p.Ile66Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I66V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPT1B NM_152246.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14551595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPT1B	NM_152246.3	c.196A>T	p.Ile66Phe	missense_variant	3/20	ENST00000312108.12
CHKB-CPT1B	NR_027928.2	n.1766A>T		non_coding_transcript_exon_variant	13/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPT1B	ENST00000312108.12	c.196A>T	p.Ile66Phe	missense_variant	3/20	1	NM_152246.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	0.0081	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	17
DANN	Benign	0.84
DEOGEN2	Uncertain	0.57	D;D;D;D;.;.
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.73
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.15	T;T;T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	-0.34	N;N;N;N;N;.
MutationTaster	Benign	0.98	P;P;P;P;P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.3	N;N;N;N;N;D
REVEL	Benign	0.24
Sift	Benign	0.28	T;T;T;T;T;T
Sift4G	Benign	0.18	T;T;T;T;T;.
Polyphen		0.14	B;B;B;B;.;.
Vest4		0.31
MutPred		0.38		Gain of catalytic residue at I66 (P = 0.0882);Gain of catalytic residue at I66 (P = 0.0882);Gain of catalytic residue at I66 (P = 0.0882);Gain of catalytic residue at I66 (P = 0.0882);Gain of catalytic residue at I66 (P = 0.0882);Gain of catalytic residue at I66 (P = 0.0882);
MVP		0.49
ClinPred		0.29	T
GERP RS		0.88
Varity_R		0.096
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3213445; hg19: chr22-51015838;