rs1056425

Variant names:

• chr1-53214418-G-A
• rs1056425
• ENST00000470385.5:n.966C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000470385.5(CZIB):​n.966C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 486,566 control chromosomes in the GnomAD database, including 23,146 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 0.25 (5976 hom., cov: 33)
  • Exomes 𝑓: 0.31 (17170 hom.)
• Consequence: CZIB ENST00000470385.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 17 publications found

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]

CPT2 Gene-Disease associations (from GenCC):

• carnitine palmitoyltransferase II deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Myriad Women’s Health
• carnitine palmitoyl transferase II deficiency, myopathic form

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia
• carnitine palmitoyl transferase II deficiency, neonatal form

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia
• carnitine palmitoyl transferase II deficiency, severe infantile form

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet
• encephalopathy, acute, infection-induced, susceptibility to, 4

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CZIB	NM_017887.3	c.*241C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000294360.5	NP_060357.1
CPT2	NM_000098.3	c.*823G>A		downstream_gene_variant		ENST00000371486.4	NP_000089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CZIB	ENST00000294360.5	c.*241C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_017887.3	ENSP00000294360.4
CPT2	ENST00000371486.4	c.*823G>A		downstream_gene_variant		1	NM_000098.3	ENSP00000360541.3

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38661 AN: 151980 Hom.: 5971 Cov.: 33

Gnomad AFR AF: 0.0928

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.307 AC: 102770 AN: 334468 Hom.: 17170 Cov.: 2 AF XY: 0.301 AC XY: 52145 AN XY: 172960

African (AFR) AF: 0.0908 AC: 982 AN: 10818

American (AMR) AF: 0.247 AC: 3659 AN: 14796

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 2486 AN: 10890

East Asian (EAS) AF: 0.455 AC: 12147 AN: 26710

South Asian (SAS) AF: 0.162 AC: 3862 AN: 23802

European-Finnish (FIN) AF: 0.387 AC: 8814 AN: 22764

Middle Eastern (MID) AF: 0.181 AC: 281 AN: 1550

European-Non Finnish (NFE) AF: 0.320 AC: 64817 AN: 202800

Other (OTH) AF: 0.281 AC: 5722 AN: 20338

GnomAD4 genome AF: 0.254 AC: 38672 AN: 152098 Hom.: 5976 Cov.: 33 AF XY: 0.257 AC XY: 19100 AN XY: 74320

African (AFR) AF: 0.0928 AC: 3851 AN: 41508

American (AMR) AF: 0.240 AC: 3666 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 828 AN: 3472

East Asian (EAS) AF: 0.440 AC: 2269 AN: 5160

South Asian (SAS) AF: 0.166 AC: 802 AN: 4824

European-Finnish (FIN) AF: 0.406 AC: 4280 AN: 10550

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22020 AN: 67974

Other (OTH) AF: 0.226 AC: 478 AN: 2112

Alfa AF: 0.287 Hom.: 8514

Bravo AF: 0.237

Asia WGS AF: 0.298 AC: 1034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.72
PhyloP100		1.2
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: rs1056425; hg19: chr1-53680090;