Variant 9-128191895-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001257975.2(CIZ1):c.45G>T(p.Ala15Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 1,445,730 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0046 ( 15 hom. )

Consequence

CIZ1
NM_001257975.2 synonymous

Scores

Clinical Significance

Benign/Likely benign no assertion criteria provided B:3

Conservation

PhyloP100: 1.32

Variant links:

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 links:

DNM1 (HGNC:):

DNM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 9-128191895-C-A is Benign according to our data. Variant chr9-128191895-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1174752.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-128191895-C-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.32 with no splicing effect.

BS2

High AC in GnomAd4 at 553 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
CIZ1	NM_001257975.2 linkuse as main transcript	c.45G>T	p.Ala15Ala	synonymous_variant	1/18	NP_001244904.1	Q9ULV3F5H2X7B7Z3U7
CIZ1	NM_012127.3 linkuse as main transcript	c.-5-1033G>T		intron_variant		NP_036259.2	Q9ULV3-1A0A024R885
CIZ1	NM_001131015.2 linkuse as main transcript	c.-5-1033G>T		intron_variant		NP_001124487.1	Q9ULV3-4Q9BTG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
CIZ1	ENST00000538431.5 linkuse as main transcript	c.45G>T	p.Ala15Ala	synonymous_variant	1/18	2	ENSP00000439244.2	F5H2X7
CIZ1	ENST00000634901.1 linkuse as main transcript	c.-5-1033G>T		intron_variant		5	ENSP00000489425.1	Q9ULV3-1
CIZ1	ENST00000372948.7 linkuse as main transcript	c.-5-1033G>T		intron_variant		2	ENSP00000362039.3	Q9ULV3-4

Frequencies

GnomAD3 genomes

AF:

0.00364

AC:

553

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0128

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00516

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00250

AC:

178

AN:

71106

Hom.:

AF XY:

0.00257

AC XY:

105

AN XY:

40824

show subpopulations

Gnomad AFR exome

AF:

0.000705

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000188

Gnomad FIN exome

AF:

0.0164

Gnomad NFE exome

AF:

0.00409

Gnomad OTH exome

AF:

0.000949

GnomAD4 exome

AF:

0.00458

AC:

5927

AN:

1293540

Hom.:

Cov.:

AF XY:

0.00432

AC XY:

2745

AN XY:

635972

show subpopulations

Gnomad4 AFR exome

AF:

0.000708

Gnomad4 AMR exome

AF:

0.000774

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000199

Gnomad4 FIN exome

AF:

0.0127

Gnomad4 NFE exome

AF:

0.00510

Gnomad4 OTH exome

AF:

0.00409

GnomAD4 genome

AF:

0.00363

AC:

553

AN:

152190

Hom.:

Cov.:

AF XY:

0.00378

AC XY:

281

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0128

Gnomad4 NFE

AF:

0.00516

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00159

Hom.:

Bravo

AF:

0.00284

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

CIZ1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.92

Splicing

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