chr22-50570881-C-T

Variant names:

• chr22-50570881-C-T
• rs186124477
• NM_152246.3:c.2028+10G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_152246.3(CPT1B):​c.2028+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,612,388 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00073 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (1 hom.)
• Consequence: CPT1B NM_152246.3 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.674
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 22-50570881-C-T is Benign according to our data. Variant chr22-50570881-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3050154.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1B	NM_152246.3	c.2028+10G>A		intron_variant	Intron 16 of 19	ENST00000312108.12	NP_689452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1B	ENST00000312108.12	c.2028+10G>A		intron_variant	Intron 16 of 19	1	NM_152246.3	ENSP00000312189.8
CHKB-CPT1B	ENST00000453634.5	n.*2253+10G>A		intron_variant	Intron 19 of 22	5		ENSP00000457031.1

Frequencies

GnomAD3 genomes AF: 0.000729 AC: 111 AN: 152228 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000765 AC: 190 AN: 248306 AF XY: 0.000743

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000721

Gnomad OTH exome AF: 0.000655

GnomAD4 exome AF: 0.00111 AC: 1615 AN: 1460042 Hom.: 1 Cov.: 32 AF XY: 0.00106 AC XY: 772 AN XY: 726242

African (AFR) AF: 0.000329 AC: 11 AN: 33466

American (AMR) AF: 0.00289 AC: 129 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0000768 AC: 2 AN: 26058

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52646

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5732

European-Non Finnish (NFE) AF: 0.00124 AC: 1383 AN: 1111244

Other (OTH) AF: 0.00136 AC: 82 AN: 60330

GnomAD4 genome AF: 0.000729 AC: 111 AN: 152346 Hom.: 1 Cov.: 33 AF XY: 0.000604 AC XY: 45 AN XY: 74494

African (AFR) AF: 0.000409 AC: 17 AN: 41576

American (AMR) AF: 0.00196 AC: 30 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68036

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000479 Hom.: 0

Bravo AF: 0.00108

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CPT1B-related disorder Benign:1

Sep 08, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.7
DANN	Benign	0.39
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs186124477; hg19: chr22-51009310;