rs45611034

chr9-128170094-T-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001131016.2(CIZ1):c.1957A>C(p.Arg653=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,605,114 control chromosomes in the GnomAD database, including 462 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (36 hom., cov: 33)
  • Exomes 𝑓: 0.022 (426 hom.)
• Consequence: CIZ1 NM_001131016.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16

Genes affected

CIZ1 (HGNC:16744): (CDKN1A interacting zinc finger protein 1) The protein encoded by this gene is a zinc finger DNA binding protein that interacts with CIP1, part of a complex with cyclin E. The encoded protein may regulate the cellular localization of CIP1. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 9-128170094-T-G is Benign according to our data. Variant chr9-128170094-T-G is described in ClinVar as [Benign]. Clinvar id is 413832.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-128170094-T-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.16 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.02 (2870/143754) while in subpopulation AMR AF= 0.0286 (381/13318). AF 95% confidence interval is 0.0264. There are 36 homozygotes in gnomad4. There are 1373 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2871 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIZ1	NM_001131016.2	c.1957A>C	p.Arg653=	synonymous_variant	12/17	ENST00000372938.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIZ1	ENST00000372938.10	c.1957A>C	p.Arg653=	synonymous_variant	12/17	1	NM_001131016.2	P2

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 2871 AN: 143632 Hom.: 36 Cov.: 33

Gnomad AFR AF: 0.00436

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0287

Gnomad ASJ AF: 0.0379

Gnomad EAS AF: 0.000203

Gnomad SAS AF: 0.0131

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.0762

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0279

GnomAD3 exomes AF: 0.0189 AC: 4677 AN: 248022 Hom.: 59 AF XY: 0.0196 AC XY: 2636 AN XY: 134326

Gnomad AFR exome AF: 0.00388

Gnomad AMR exome AF: 0.0166

Gnomad ASJ exome AF: 0.0360

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0110

Gnomad FIN exome AF: 0.0139

Gnomad NFE exome AF: 0.0259

Gnomad OTH exome AF: 0.0253

GnomAD4 exome AF: 0.0216 AC: 31592 AN: 1461360 Hom.: 426 Cov.: 32 AF XY: 0.0217 AC XY: 15746 AN XY: 727022

Gnomad4 AFR exome AF: 0.00454

Gnomad4 AMR exome AF: 0.0164

Gnomad4 ASJ exome AF: 0.0365

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0111

Gnomad4 FIN exome AF: 0.0145

Gnomad4 NFE exome AF: 0.0237

Gnomad4 OTH exome AF: 0.0226

GnomAD4 genome AF: 0.0200 AC: 2870 AN: 143754 Hom.: 36 Cov.: 33 AF XY: 0.0197 AC XY: 1373 AN XY: 69638

Gnomad4 AFR AF: 0.00435

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.0379

Gnomad4 EAS AF: 0.000203

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.0162

Gnomad4 NFE AF: 0.0275

Gnomad4 OTH AF: 0.0281

Alfa AF: 0.0231 Hom.: 18

Bravo AF: 0.0191

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.0309

EpiControl AF: 0.0303

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dystonic disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	9.3
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs45611034; hg19: chr9-130932373;