1-53214206-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017887.3(CZIB):c.*453A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 164,476 control chromosomes in the GnomAD database, including 6,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (6034 hom., cov: 33)
  • Exomes 𝑓: 0.28 (592 hom.)
• Consequence: CZIB NM_017887.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.276

Genes affected

CZIB (HGNC:26059): (CXXC motif containing zinc binding protein) Enables zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

CPT2 (HGNC:2330): (carnitine palmitoyltransferase 2) The protein encoded by this gene is a nuclear protein which is transported to the mitochondrial inner membrane. Together with carnitine palmitoyltransferase I, the encoded protein oxidizes long-chain fatty acids in the mitochondria. Defects in this gene are associated with mitochondrial long-chain fatty-acid (LCFA) oxidation disorders. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-53214206-T-C is Benign according to our data. Variant chr1-53214206-T-C is described in ClinVar as [Benign]. Clinvar id is 368876.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CZIB	NM_017887.3	c.*453A>G		3_prime_UTR_variant	8/8	ENST00000294360.5
CPT2	NM_000098.3			downstream_gene_variant		ENST00000371486.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CZIB	ENST00000294360.5	c.*453A>G		3_prime_UTR_variant	8/8	1	NM_017887.3	P1
CPT2	ENST00000371486.4			downstream_gene_variant		1	NM_000098.3	P1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38790 AN: 152070 Hom.: 6029 Cov.: 33

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.284 AC: 3493 AN: 12288 Hom.: 592 Cov.: 0 AF XY: 0.273 AC XY: 1735 AN XY: 6344

Gnomad4 AFR exome AF: 0.0746

Gnomad4 AMR exome AF: 0.237

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.404

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.399

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.255 AC: 38801 AN: 152188 Hom.: 6034 Cov.: 33 AF XY: 0.258 AC XY: 19176 AN XY: 74394

Gnomad4 AFR AF: 0.0927

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.227

Alfa AF: 0.289 Hom.: 1631

Bravo AF: 0.238

Asia WGS AF: 0.303 AC: 1050 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Carnitine palmitoyltransferase II deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.8
Dann	Benign	0.49

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: rs1056438; hg19: chr1-53679878;