1-10639083-CTCGTCG-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001079843.3(CASZ1):c.5133_5138del(p.Asp1711_Asp1712del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0402 in 1,146,490 control chromosomes in the GnomAD database, including 1,261 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (241 hom., cov: 31)
  • Exomes 𝑓: 0.039 (1020 hom.)
• Consequence: CASZ1 NM_001079843.3 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:2
• Conservation: PhyloP100: 4.45

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 -16 ACMG points.

• BP6: Variant 1-10639083-CTCGTCG-C is Benign according to our data. Variant chr1-10639083-CTCGTCG-C is described in ClinVar as [Benign]. Clinvar id is 1225114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASZ1	NM_001079843.3	c.5133_5138del	p.Asp1711_Asp1712del	inframe_deletion	21/21	ENST00000377022.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASZ1	ENST00000377022.8	c.5133_5138del	p.Asp1711_Asp1712del	inframe_deletion	21/21	1	NM_001079843.3	P1

Frequencies

GnomAD3 genomes AF: 0.0473 AC: 6909 AN: 146020 Hom.: 241 Cov.: 31

Gnomad AFR AF: 0.0726

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.0569

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0268

Gnomad MID AF: 0.0695

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.0419

GnomAD3 exomes AF: 0.0336 AC: 3119 AN: 92704 Hom.: 138 AF XY: 0.0379 AC XY: 2021 AN XY: 53322

Gnomad AFR exome AF: 0.0342

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.0174

Gnomad EAS exome AF: 0.0321

Gnomad SAS exome AF: 0.0835

Gnomad FIN exome AF: 0.0278

Gnomad NFE exome AF: 0.0252

Gnomad OTH exome AF: 0.0218

GnomAD4 exome AF: 0.0391 AC: 39147 AN: 1000446 Hom.: 1020 AF XY: 0.0395 AC XY: 19159 AN XY: 485422

Gnomad4 AFR exome AF: 0.0748

Gnomad4 AMR exome AF: 0.0147

Gnomad4 ASJ exome AF: 0.0196

Gnomad4 EAS exome AF: 0.0320

Gnomad4 SAS exome AF: 0.0887

Gnomad4 FIN exome AF: 0.0298

Gnomad4 NFE exome AF: 0.0363

Gnomad4 OTH exome AF: 0.0495

GnomAD4 genome AF: 0.0473 AC: 6904 AN: 146044 Hom.: 241 Cov.: 31 AF XY: 0.0466 AC XY: 3309 AN XY: 71042

Gnomad4 AFR AF: 0.0726

Gnomad4 AMR AF: 0.0307

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.0566

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0268

Gnomad4 NFE AF: 0.0341

Gnomad4 OTH AF: 0.0415

Alfa AF: 0.00468 Hom.: 4

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Neutrophil inclusion bodies Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Phenosystems SA

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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: rs201089181; hg19: chr1-10699140;