rs45579839

Variant names:

• chr9-128180510-C-T
• rs45579839
• NM_001131016.2:c.696G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-128180510-C-T
• chr9-128180510-C-A
• chr9-128180510-C-G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001131016.2(CIZ1):​c.696G>A​(p.Pro232Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,613,958 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (18 hom.)
• Consequence: CIZ1 NM_001131016.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.607
• Publications: 2 publications found

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]

CIZ1 Gene-Disease associations (from GenCC):

• dystonia 23

  Inheritance: Unknown Classification: MODERATE Submitted by: Genomics England PanelApp
• inherited dystonia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-128180510-C-T is Benign according to our data. Variant chr9-128180510-C-T is described in ClinVar as Benign. ClinVar VariationId is 413830.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.607 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00133 (202/152206) while in subpopulation EAS AF = 0.0197 (102/5170). AF 95% confidence interval is 0.0166. There are 2 homozygotes in GnomAd4. There are 101 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 202 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001131016.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIZ1	NM_001131016.2	MANE Select	c.696G>A	p.Pro232Pro	synonymous	Exon 7 of 17	NP_001124488.1	Q9ULV3-1
	CIZ1	NM_001257975.2		c.786G>A	p.Pro262Pro	synonymous	Exon 7 of 18	NP_001244904.1	F5H2X7
	CIZ1	NM_012127.3		c.696G>A	p.Pro232Pro	synonymous	Exon 7 of 17	NP_036259.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIZ1	ENST00000372938.10	TSL:1 MANE Select	c.696G>A	p.Pro232Pro	synonymous	Exon 7 of 17	ENSP00000362029.5	Q9ULV3-1
	CIZ1	ENST00000415526.5	TSL:1	c.462G>A	p.Pro154Pro	synonymous	Exon 5 of 15	ENSP00000398011.1	H0Y5D5
	CIZ1	ENST00000372954.5	TSL:1	c.624G>A	p.Pro208Pro	synonymous	Exon 6 of 17	ENSP00000362045.1	Q9ULV3-3

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 206 AN: 152088 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0203

Gnomad SAS AF: 0.00229

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00335 AC: 841 AN: 251318 AF XY: 0.00286

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0120

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.0200

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00112 AC: 1636 AN: 1461752 Hom.: 18 Cov.: 31 AF XY: 0.00106 AC XY: 774 AN XY: 727184

African (AFR) AF: 0.000299 AC: 10 AN: 33478

American (AMR) AF: 0.0104 AC: 464 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0231 AC: 916 AN: 39694

South Asian (SAS) AF: 0.000591 AC: 51 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5768

European-Non Finnish (NFE) AF: 0.000107 AC: 119 AN: 1111908

Other (OTH) AF: 0.00101 AC: 61 AN: 60392

GnomAD4 genome AF: 0.00133 AC: 202 AN: 152206 Hom.: 2 Cov.: 32 AF XY: 0.00136 AC XY: 101 AN XY: 74400

African (AFR) AF: 0.000241 AC: 10 AN: 41524

American (AMR) AF: 0.00399 AC: 61 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0197 AC: 102 AN: 5170

South Asian (SAS) AF: 0.00229 AC: 11 AN: 4806

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68010

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000457 Hom.: 0

Bravo AF: 0.00193

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Dystonic disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.56
PhyloP100		-0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

Other links and lift over

dbSNP: rs45579839; hg19: chr9-130942789; COSMIC: COSV99476795; COSMIC: COSV99476795;