NM_152246.3:c.282-18C>T

Variant names:

• chr22-50577052-G-A
• rs131759
• NM_152246.3:c.282-18C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 9 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 (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152246.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1B	NM_152246.3	MANE Select	c.282-18C>T		intron	N/A	NP_689452.1
	CPT1B	NM_001145135.2		c.282-18C>T		intron	N/A	NP_001138607.1
	CPT1B	NM_001145137.2		c.282-18C>T		intron	N/A	NP_001138609.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT1B	ENST00000312108.12	TSL:1 MANE Select	c.282-18C>T		intron	N/A	ENSP00000312189.8
	CPT1B	ENST00000395650.6	TSL:1	c.282-18C>T		intron	N/A	ENSP00000379011.2
	CPT1B	ENST00000405237.7	TSL:1	c.282-18C>T		intron	N/A	ENSP00000385486.3

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

GnomAD2 exomes AF: 0.443 AC: 109437 AN: 247292 AF XY: 0.443

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 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

African (AFR) AF: 0.125 AC: 4163 AN: 33422

American (AMR) AF: 0.463 AC: 20672 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 11527 AN: 26104

East Asian (EAS) AF: 0.467 AC: 18513 AN: 39666

South Asian (SAS) AF: 0.367 AC: 31624 AN: 86226

European-Finnish (FIN) AF: 0.521 AC: 27618 AN: 52988

Middle Eastern (MID) AF: 0.355 AC: 1994 AN: 5614

European-Non Finnish (NFE) AF: 0.488 AC: 542221 AN: 1110714

Other (OTH) AF: 0.441 AC: 26581 AN: 60300

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

African (AFR) AF: 0.139 AC: 5794 AN: 41564

American (AMR) AF: 0.433 AC: 6612 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1533 AN: 3472

East Asian (EAS) AF: 0.460 AC: 2367 AN: 5150

South Asian (SAS) AF: 0.360 AC: 1736 AN: 4816

European-Finnish (FIN) AF: 0.527 AC: 5584 AN: 10590

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32755 AN: 67984

Other (OTH) AF: 0.388 AC: 818 AN: 2110

Alfa AF: 0.420 Hom.: 4079

Bravo AF: 0.369

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.57
PhyloP100		-0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs131759; hg19: chr22-51015481; COSMIC: COSV56418949; COSMIC: COSV56418949;