rs131759

Positions:

• chr22-50577052-G-A
• chr22-50577052-G-C

Variant summary

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

The NM_152246.3(CPT1B):​c.282-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,611,884 control chromosomes in the GnomAD database, including 176,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.38 (12744 hom., cov: 33)
  • Exomes 𝑓: 0.47 (164044 hom.)
• Consequence: CPT1B NM_152246.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

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 (BayesDel_noAF=-0.87).
• BP6: Variant 22-50577052-G-A is Benign according to our data. Variant chr22-50577052-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPT1B	NM_152246.3	c.282-18C>T		intron_variant		ENST00000312108.12	NP_689452.1
CHKB-CPT1B	NR_027928.2	n.1852-18C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPT1B	ENST00000312108.12	c.282-18C>T		intron_variant		1	NM_152246.3	ENSP00000312189	P1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57800 AN: 152058 Hom.: 12750 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.390

GnomAD3 exomes AF: 0.443 AC: 109437 AN: 247292 Hom.: 25346 AF XY: 0.443 AC XY: 59479 AN XY: 134156

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.464

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.454

Gnomad SAS exome AF: 0.359

Gnomad FIN exome AF: 0.529

Gnomad NFE exome AF: 0.485

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.469 AC: 684913 AN: 1459708 Hom.: 164044 Cov.: 48 AF XY: 0.466 AC XY: 338492 AN XY: 725938

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.442

Gnomad4 EAS exome AF: 0.467

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.441

GnomAD4 genome AF: 0.380 AC: 57795 AN: 152176 Hom.: 12744 Cov.: 33 AF XY: 0.383 AC XY: 28481 AN XY: 74390

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.388

Alfa AF: 0.425 Hom.: 4066

Bravo AF: 0.369

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs131759; hg19: chr22-51015481; COSMIC: COSV56418949; COSMIC: COSV56418949;