rs5770911

Positions:

• chr22-50572812-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152246.3(CPT1B):​c.1352+63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,532,640 control chromosomes in the GnomAD database, including 4,509 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 0.064 (499 hom., cov: 33)
  • Exomes 𝑓: 0.061 (4010 hom.)
• Consequence: CPT1B NM_152246.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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]

CPT1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1B	NM_152246.3	c.1352+63G>A		intron_variant		ENST00000312108.12	NP_689452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1B	ENST00000312108.12	c.1352+63G>A		intron_variant		1	NM_152246.3	ENSP00000312189.8
CHKB-CPT1B	ENST00000453634.5	n.*1583+63G>A		intron_variant		5		ENSP00000457031.1

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9728 AN: 152148 Hom.: 499 Cov.: 33

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0554

GnomAD4 exome AF: 0.0608 AC: 83991 AN: 1380374 Hom.: 4010 AF XY: 0.0619 AC XY: 42228 AN XY: 682418

Gnomad4 AFR exome AF: 0.0468

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.0439

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.0536

Gnomad4 NFE exome AF: 0.0469

Gnomad4 OTH exome AF: 0.0661

GnomAD4 genome AF: 0.0640 AC: 9743 AN: 152266 Hom.: 499 Cov.: 33 AF XY: 0.0664 AC XY: 4946 AN XY: 74442

Gnomad4 AFR AF: 0.0495

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0424

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0521

Gnomad4 NFE AF: 0.0477

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0537 Hom.: 519

Bravo AF: 0.0689

Asia WGS AF: 0.178 AC: 620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.53
DANN	Benign	0.72

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: rs5770911; hg19: chr22-51011241;