rs144814370

Variant names:

• chr9-128191895-C-A
• rs144814370
• NM_001257975.2:c.45G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-128191895-C-A
• chr9-128191895-C-G
• chr9-128191895-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

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
• Clinical Significance: Benign/Likely benign no assertion criteria provided B:3
• Conservation: PhyloP100: 1.32

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]

DNM1 (HGNC:2972): (dynamin 1) This gene encodes a member of the dynamin subfamily of GTP-binding proteins. The encoded protein possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the encoded protein, which can also self-assemble leading to stimulation of GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, particularly on chromosomes Y and 15. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

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 rank	MANE	Protein	UniProt
CIZ1	NM_001257975.2	c.45G>T	p.Ala15Ala	synonymous_variant	Exon 1 of 18		NP_001244904.1
CIZ1	NM_012127.3	c.-5-1033G>T		intron_variant	Intron 1 of 16		NP_036259.2
CIZ1	NM_001131015.2	c.-5-1033G>T		intron_variant	Intron 1 of 17		NP_001124487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIZ1	ENST00000538431.5	c.45G>T	p.Ala15Ala	synonymous_variant	Exon 1 of 18	2		ENSP00000439244.2
CIZ1	ENST00000634901.1	c.-5-1033G>T		intron_variant	Intron 4 of 19	5		ENSP00000489425.1
CIZ1	ENST00000372948.7	c.-5-1033G>T		intron_variant	Intron 1 of 17	2		ENSP00000362039.3

Frequencies

GnomAD3 genomes AF: 0.00364 AC: 553 AN: 152072 Hom.: 3 Cov.: 31

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.: 2 AF XY: 0.00257 AC XY: 105 AN XY: 40824

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.: 15 Cov.: 31 AF XY: 0.00432 AC XY: 2745 AN XY: 635972

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.: 3 Cov.: 31 AF XY: 0.00378 AC XY: 281 AN XY: 74412

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.: 0

Bravo AF: 0.00284

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:2

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

CIZ1-related disorder Benign:1

Oct 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	15
DANN	Benign	0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs144814370; hg19: chr9-130954174;