22-50572947-G-C

Position:

• chr22-50572947-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000312108.12(CPT1B):​c.1280C>G​(p.Ser427Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,613,278 control chromosomes in the GnomAD database, including 38,234 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.29 (9463 hom., cov: 33)
  • Exomes 𝑓: 0.16 (28771 hom.)
• Consequence: CPT1B ENST00000312108.12 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.5282148E-5).
• BP6: Variant 22-50572947-G-C is Benign according to our data. Variant chr22-50572947-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1B	NM_152246.3	c.1280C>G	p.Ser427Cys	missense_variant	11/20	ENST00000312108.12	NP_689452.1
CHKB-CPT1B	NR_027928.2	n.2850C>G		non_coding_transcript_exon_variant	21/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1B	ENST00000312108.12	c.1280C>G	p.Ser427Cys	missense_variant	11/20	1	NM_152246.3	ENSP00000312189	P1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43633 AN: 152076 Hom.: 9422 Cov.: 33

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.234

GnomAD3 exomes AF: 0.243 AC: 60397 AN: 248986 Hom.: 10514 AF XY: 0.233 AC XY: 31474 AN XY: 134812

Gnomad AFR exome AF: 0.595

Gnomad AMR exome AF: 0.318

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.518

Gnomad SAS exome AF: 0.359

Gnomad FIN exome AF: 0.195

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.160 AC: 233635 AN: 1461084 Hom.: 28771 Cov.: 33 AF XY: 0.163 AC XY: 118799 AN XY: 726806

Gnomad4 AFR exome AF: 0.607

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.493

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.287 AC: 43736 AN: 152194 Hom.: 9463 Cov.: 33 AF XY: 0.295 AC XY: 21933 AN XY: 74416

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.243

Alfa AF: 0.116 Hom.: 499

Bravo AF: 0.302

TwinsUK AF: 0.111 AC: 410

ALSPAC AF: 0.119 AC: 459

ESP6500AA AF: 0.565 AC: 2491

ESP6500EA AF: 0.117 AC: 1004

ExAC AF: 0.244 AC: 29660

Asia WGS AF: 0.500 AC: 1739 AN: 3478

EpiCase AF: 0.114

EpiControl AF: 0.117

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	1.5
DANN	Benign	0.55
DEOGEN2	Uncertain	0.68	D;D;D;D;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00089	N
LIST_S2	Benign	0.053	.;.;.;T;T
MetaRNN	Benign	0.000055	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N;N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.7	N;N;N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.23	T;T;T;T;T
Sift4G	Benign	0.069	T;T;T;T;T
Polyphen		0.0	B;B;B;B;.
Vest4		0.051
ClinPred		0.0054	T
GERP RS		-5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.062
gMVP		0.49

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: rs8142477; hg19: chr22-51011376; COSMIC: COSV56416808; COSMIC: COSV56416808;