1-10639086-GTCGTCGTCGTCC-G

Position:

• chr1-10639086-GTCGTCGTCGTCC-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The ENST00000377022.8(CASZ1):​c.5124_5135del​(p.Glu1708_Asp1711del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00686 in 1,048,700 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0070 (21 hom.)
• Consequence: CASZ1 ENST00000377022.8 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.47

Genes affected

CASZ1 (HGNC:26002): (castor zinc finger 1) The protein encoded by this gene is a zinc finger transcription factor. The encoded protein may function as a tumor suppressor, and single nucleotide polymorphisms in this gene are associated with blood pressure variation. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 1-10639086-GTCGTCGTCGTCC-G is Benign according to our data. Variant chr1-10639086-GTCGTCGTCGTCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 774786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 769 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASZ1	NM_001079843.3	c.5124_5135del	p.Glu1708_Asp1711del	inframe_deletion	21/21	ENST00000377022.8	NP_001073312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASZ1	ENST00000377022.8	c.5124_5135del	p.Glu1708_Asp1711del	inframe_deletion	21/21	1	NM_001079843.3	ENSP00000366221	P1

Frequencies

GnomAD3 genomes AF: 0.00581 AC: 770 AN: 132574 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00112

Gnomad AMR AF: 0.00643

Gnomad ASJ AF: 0.00156

Gnomad EAS AF: 0.00576

Gnomad SAS AF: 0.00828

Gnomad FIN AF: 0.00163

Gnomad MID AF: 0.0155

Gnomad NFE AF: 0.00819

Gnomad OTH AF: 0.00923

GnomAD3 exomes AF: 0.00231 AC: 210 AN: 91066 Hom.: 1 AF XY: 0.00246 AC XY: 129 AN XY: 52464

Gnomad AFR exome AF: 0.00136

Gnomad AMR exome AF: 0.000308

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000935

Gnomad SAS exome AF: 0.00305

Gnomad FIN exome AF: 0.00165

Gnomad NFE exome AF: 0.00325

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00701 AC: 6422 AN: 916090 Hom.: 21 AF XY: 0.00684 AC XY: 3033 AN XY: 443430

Gnomad4 AFR exome AF: 0.00176

Gnomad4 AMR exome AF: 0.000983

Gnomad4 ASJ exome AF: 0.000698

Gnomad4 EAS exome AF: 0.00353

Gnomad4 SAS exome AF: 0.00658

Gnomad4 FIN exome AF: 0.00178

Gnomad4 NFE exome AF: 0.00755

Gnomad4 OTH exome AF: 0.00578

GnomAD4 genome AF: 0.00580 AC: 769 AN: 132610 Hom.: 4 Cov.: 31 AF XY: 0.00540 AC XY: 349 AN XY: 64594

Gnomad4 AFR AF: 0.00234

Gnomad4 AMR AF: 0.00642

Gnomad4 ASJ AF: 0.00156

Gnomad4 EAS AF: 0.00578

Gnomad4 SAS AF: 0.00777

Gnomad4 FIN AF: 0.00163

Gnomad4 NFE AF: 0.00819

Gnomad4 OTH AF: 0.00969

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	CASZ1: BS1, BS2 -

CASZ1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 10, 2022

This variant is classified as likely 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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs770782033; hg19: chr1-10699143;