22-50572947-G-C

Variant names:

• chr22-50572947-G-C
• rs8142477
• NM_152246.3:c.1280C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152246.3(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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (9463 hom., cov: 33)
  • Exomes 𝑓: 0.16 (28771 hom.)
• Consequence: CPT1B NM_152246.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 35 publications found

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:41998): (CHKB-CPT1B readthrough (NMD candidate)) The genes CHKB and CPT1B are adjacent on chromosome 22 and read-through transcripts are expressed that include exons from both loci. The read-through transcripts are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to express proteins. [provided by RefSeq, Jun 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.5282148E-5).
• 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 rank	MANE	Protein	UniProt
CPT1B	NM_152246.3	c.1280C>G	p.Ser427Cys	missense_variant	Exon 11 of 20	ENST00000312108.12	NP_689452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1B	ENST00000312108.12	c.1280C>G	p.Ser427Cys	missense_variant	Exon 11 of 20	1	NM_152246.3	ENSP00000312189.8
CHKB-CPT1B	ENST00000453634.5	n.*1511C>G		non_coding_transcript_exon_variant	Exon 14 of 23	5		ENSP00000457031.1
CHKB-CPT1B	ENST00000453634.5	n.*1511C>G		3_prime_UTR_variant	Exon 14 of 23	5		ENSP00000457031.1

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

GnomAD2 exomes AF: 0.243 AC: 60397 AN: 248986 AF XY: 0.233

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 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

African (AFR) AF: 0.607 AC: 20318 AN: 33466

American (AMR) AF: 0.310 AC: 13877 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 3051 AN: 26136

East Asian (EAS) AF: 0.493 AC: 19572 AN: 39668

South Asian (SAS) AF: 0.354 AC: 30491 AN: 86238

European-Finnish (FIN) AF: 0.188 AC: 10004 AN: 53210

Middle Eastern (MID) AF: 0.163 AC: 941 AN: 5762

European-Non Finnish (NFE) AF: 0.112 AC: 123992 AN: 1111524

Other (OTH) AF: 0.189 AC: 11389 AN: 60366

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

African (AFR) AF: 0.582 AC: 24160 AN: 41504

American (AMR) AF: 0.262 AC: 4005 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3468

East Asian (EAS) AF: 0.508 AC: 2631 AN: 5178

South Asian (SAS) AF: 0.379 AC: 1830 AN: 4824

European-Finnish (FIN) AF: 0.204 AC: 2160 AN: 10594

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7850 AN: 67998

Other (OTH) AF: 0.243 AC: 514 AN: 2116

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;.
PhyloP100		0.60
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
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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