Genetic Variant CZIB:c.*457C>A (chr1-53214202-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.431

Variant links:

Genes affected

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

CZIB links:

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]

CPT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CZIB	NM_017887.3 link	c.*457C>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000294360.5	NP_060357.1	Q9NWV4
CPT2	NM_000098.3 link	c.*607G>T		downstream_gene_variant		ENST00000371486.4	NP_000089.1	P23786A0A140VK13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CZIB	ENST00000294360 link	c.*457C>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_017887.3	ENSP00000294360.4		Q9NWV4
CPT2	ENST00000371486.4 link	c.*607G>T		downstream_gene_variant		1	NM_000098.3	ENSP00000360541.3		P23786

Frequencies

GnomAD3 genomes

AF:

0.00944

AC:

1436

AN:

152172

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00953

AC XY:

AN XY:

6718

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

200

Gnomad4 AMR exome

AF:

0.00190

AC:

AN:

2110

Gnomad4 ASJ exome

AF:

0.0133

AC:

AN:

226

Gnomad4 EAS exome

AF:

0.00568

AC:

AN:

528

Gnomad4 SAS exome

AF:

0.0244

AC:

AN:

1188

Gnomad4 FIN exome

AF:

0.00394

AC:

AN:

254

Gnomad4 NFE exome

AF:

0.00877

AC:

AN:

7754

Gnomad4 Remaining exome

AF:

0.00482

AC:

AN:

622

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00942

AC:

1435

AN:

152290

Hom.:

Cov.:

AF XY:

0.00982

AC XY:

731

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00243

AC:

0.00242964

AN:

0.00242964

Gnomad4 AMR

AF:

0.00752

AC:

0.00751634

AN:

0.00751634

Gnomad4 ASJ

AF:

0.00605

AC:

0.00605187

AN:

0.00605187

Gnomad4 EAS

AF:

0.00946

AC:

0.00945581

AN:

0.00945581

Gnomad4 SAS

AF:

0.0363

AC:

0.0362619

AN:

0.0362619

Gnomad4 FIN

AF:

0.0190

AC:

0.0190351

AN:

0.0190351

Gnomad4 NFE

AF:

0.0111

AC:

0.0110716

AN:

0.0110716

Gnomad4 OTH

AF:

0.00758

AC:

0.00757576

AN:

0.00757576

Heterozygous variant carriers

154

232

309

386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00704

Hom.:

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

LINK: link

Submissions by phenotype

Carnitine palmitoyltransferase II deficiency

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.78

DANN

Benign

0.56

Mutation Taster

=100/0

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over