9-128180530-T-C

Position:

• chr9-128180530-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001131016.2(CIZ1):​c.683-7A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,611,328 control chromosomes in the GnomAD database, including 1,477 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (705 hom., cov: 31)
  • Exomes 𝑓: 0.0077 (772 hom.)
• Consequence: CIZ1 NM_001131016.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002037
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.52

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-128180530-T-C is Benign according to our data. Variant chr9-128180530-T-C is described in ClinVar as [Benign]. Clinvar id is 413840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIZ1	NM_001131016.2	c.683-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000372938.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIZ1	ENST00000372938.10	c.683-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001131016.2	P2

Frequencies

GnomAD3 genomes AF: 0.0537 AC: 8172 AN: 152054 Hom.: 707 Cov.: 31

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0242

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0392

GnomAD3 exomes AF: 0.0180 AC: 4530 AN: 251194 Hom.: 295 AF XY: 0.0160 AC XY: 2168 AN XY: 135754

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.0114

Gnomad ASJ exome AF: 0.00527

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0316

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000810

Gnomad OTH exome AF: 0.00980

GnomAD4 exome AF: 0.00775 AC: 11303 AN: 1459156 Hom.: 772 Cov.: 29 AF XY: 0.00776 AC XY: 5637 AN XY: 726078

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.0125

Gnomad4 ASJ exome AF: 0.00502

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0296

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000458

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.0538 AC: 8184 AN: 152172 Hom.: 705 Cov.: 31 AF XY: 0.0524 AC XY: 3899 AN XY: 74420

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.0241

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0320

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0275 Hom.: 132

Bravo AF: 0.0618

Asia WGS AF: 0.0310 AC: 107 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Dystonic disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000020
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.010		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: rs45518842; hg19: chr9-130942809;