chr22-50571524-C-T

Variant names:

• chr22-50571524-C-T
• rs470117
• NM_152246.3:c.1591G>A

Variant summary

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

The NM_152246.3(CPT1B):​c.1591G>A​(p.Glu531Lys) variant causes a missense change. The variant allele was found at a frequency of 0.441 in 1,612,312 control chromosomes in the GnomAD database, including 161,958 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (11649 hom., cov: 33)
  • Exomes 𝑓: 0.45 (150309 hom.)
• Consequence: CPT1B NM_152246.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98
• Publications: 49 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=0.001192987).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1B	NM_152246.3	c.1591G>A	p.Glu531Lys	missense_variant	Exon 14 of 20	ENST00000312108.12	NP_689452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1B	ENST00000312108.12	c.1591G>A	p.Glu531Lys	missense_variant	Exon 14 of 20	1	NM_152246.3	ENSP00000312189.8
CHKB-CPT1B	ENST00000453634.5	n.*1816G>A		non_coding_transcript_exon_variant	Exon 17 of 23	5		ENSP00000457031.1
CHKB-CPT1B	ENST00000453634.5	n.*1816G>A		3_prime_UTR_variant	Exon 17 of 23	5		ENSP00000457031.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55629 AN: 151966 Hom.: 11655 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.384

GnomAD2 exomes AF: 0.424 AC: 105061 AN: 247692 AF XY: 0.424

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.458

Gnomad ASJ exome AF: 0.437

Gnomad EAS exome AF: 0.453

Gnomad FIN exome AF: 0.457

Gnomad NFE exome AF: 0.466

Gnomad OTH exome AF: 0.437

GnomAD4 exome AF: 0.449 AC: 655949 AN: 1460228 Hom.: 150309 Cov.: 59 AF XY: 0.446 AC XY: 324157 AN XY: 726472

African (AFR) AF: 0.133 AC: 4451 AN: 33474

American (AMR) AF: 0.457 AC: 20416 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 11220 AN: 26126

East Asian (EAS) AF: 0.467 AC: 18519 AN: 39696

South Asian (SAS) AF: 0.343 AC: 29619 AN: 86248

European-Finnish (FIN) AF: 0.455 AC: 23627 AN: 51956

Middle Eastern (MID) AF: 0.342 AC: 1972 AN: 5764

European-Non Finnish (NFE) AF: 0.468 AC: 520515 AN: 1111880

Other (OTH) AF: 0.424 AC: 25610 AN: 60374

GnomAD4 genome AF: 0.366 AC: 55630 AN: 152084 Hom.: 11649 Cov.: 33 AF XY: 0.366 AC XY: 27208 AN XY: 74342

African (AFR) AF: 0.145 AC: 6013 AN: 41528

American (AMR) AF: 0.425 AC: 6492 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1487 AN: 3468

East Asian (EAS) AF: 0.460 AC: 2375 AN: 5164

South Asian (SAS) AF: 0.338 AC: 1632 AN: 4828

European-Finnish (FIN) AF: 0.453 AC: 4790 AN: 10566

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31441 AN: 67940

Other (OTH) AF: 0.381 AC: 804 AN: 2108

Alfa AF: 0.419 Hom.: 29142

Bravo AF: 0.360

TwinsUK AF: 0.463 AC: 1716

ALSPAC AF: 0.455 AC: 1755

ESP6500AA AF: 0.156 AC: 689

ESP6500EA AF: 0.458 AC: 3935

ExAC AF: 0.418 AC: 50790

Asia WGS AF: 0.358 AC: 1243 AN: 3478

EpiCase AF: 0.450

EpiControl AF: 0.451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D;D;D;D;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	.;.;.;T;T
MetaRNN	Benign	0.0012	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;L;L;.
PhyloP100		4.0
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.5	D;D;D;D;N
REVEL	Uncertain	0.43
Sift	Benign	0.095	T;T;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.68	P;P;P;P;.
Vest4		0.17
ClinPred		0.016	T
GERP RS		5.3
Varity_R		0.62
gMVP		0.57
Mutation Taster		=75/25	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: rs470117; hg19: chr22-51009953; COSMIC: COSV56415928; COSMIC: COSV56415928;