chr9-128203260-A-G

Variant names:

• chr9-128203260-A-G
• rs4240427
• NM_012127.3:c.-6+926T>C

Variant summary

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

The NM_012127.3(CIZ1):​c.-6+926T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 214,822 control chromosomes in the GnomAD database, including 96,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66478 hom., cov: 32)
  • Exomes 𝑓: 0.97 (29781 hom.)
• Consequence: CIZ1 NM_012127.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.350

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-128203260-A-G is Benign according to our data. Variant chr9-128203260-A-G is described in ClinVar as [Benign]. Clinvar id is 1182484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM1	NM_004408.4	c.-211A>G		upstream_gene_variant		ENST00000372923.8	NP_004399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM1	ENST00000372923.8	c.-211A>G		upstream_gene_variant		1	NM_004408.4	ENSP00000362014.4
DNM1	ENST00000634267.2	c.-211A>G		upstream_gene_variant		5		ENSP00000489096.1

Frequencies

GnomAD3 genomes AF: 0.933 AC: 141643 AN: 151872 Hom.: 66456 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.937

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.983

Gnomad OTH AF: 0.939

GnomAD4 exome AF: 0.973 AC: 61130 AN: 62836 Hom.: 29781 AF XY: 0.974 AC XY: 32385 AN XY: 33238

Gnomad4 AFR exome AF: 0.801

Gnomad4 AMR exome AF: 0.976

Gnomad4 ASJ exome AF: 0.919

Gnomad4 EAS exome AF: 0.936

Gnomad4 SAS exome AF: 0.950

Gnomad4 FIN exome AF: 0.980

Gnomad4 NFE exome AF: 0.983

Gnomad4 OTH exome AF: 0.956

GnomAD4 genome AF: 0.932 AC: 141711 AN: 151986 Hom.: 66478 Cov.: 32 AF XY: 0.933 AC XY: 69325 AN XY: 74318

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.970

Gnomad4 ASJ AF: 0.922

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.937

Gnomad4 FIN AF: 0.983

Gnomad4 NFE AF: 0.983

Gnomad4 OTH AF: 0.940

Alfa AF: 0.961 Hom.: 10277

Bravo AF: 0.927

Asia WGS AF: 0.924 AC: 3214 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4240427; hg19: chr9-130965539;