1-53214202-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017887.3(CZIB):c.*457C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00936 in 165,186 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0094 (10 hom., cov: 33)
  • Exomes 𝑓: 0.0086 (1 hom.)
• Consequence: CZIB NM_017887.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.431

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=-0.84).
• BP6: Variant 1-53214202-G-T is Benign according to our data. Variant chr1-53214202-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 368875.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00942 (1435/152290) while in subpopulation SAS AF= 0.0363 (175/4826). AF 95% confidence interval is 0.0319. There are 10 homozygotes in gnomad4. There are 731 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CZIB	NM_017887.3	c.*457C>A		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.*457C>A		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: 0.00944 AC: 1436 AN: 152172 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.00244

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00753

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.0364

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.00766

GnomAD4 exome AF: 0.00861 AC: 111 AN: 12896 Hom.: 1 Cov.: 0 AF XY: 0.00953 AC XY: 64 AN XY: 6718

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.0133

Gnomad4 EAS exome AF: 0.00568

Gnomad4 SAS exome AF: 0.0244

Gnomad4 FIN exome AF: 0.00394

Gnomad4 NFE exome AF: 0.00877

Gnomad4 OTH exome AF: 0.00482

GnomAD4 genome AF: 0.00942 AC: 1435 AN: 152290 Hom.: 10 Cov.: 33 AF XY: 0.00982 AC XY: 731 AN XY: 74458

Gnomad4 AFR AF: 0.00243

Gnomad4 AMR AF: 0.00752

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00946

Gnomad4 SAS AF: 0.0363

Gnomad4 FIN AF: 0.0190

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00708 Hom.: 1

Bravo AF: 0.00671

Asia WGS AF: 0.0330 AC: 113 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Carnitine palmitoyltransferase II deficiency Benign:1

Likely 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	-0.84
Cadd	Benign	0.78
Dann	Benign	0.56

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: rs14829; hg19: chr1-53679874;