1-10638911-A-AGGCCGC

Position:

• chr1-10638911-A-AGGCCGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000377022.8(CASZ1):​c.*30_*31insGCGGCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.047 in 948,280 control chromosomes in the GnomAD database, including 1,444 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (566 hom., cov: 31)
  • Exomes 𝑓: 0.043 (878 hom.)
• Consequence: CASZ1 ENST00000377022.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.863

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 -10 ACMG points.

• BP6: Variant 1-10638911-A-AGGCCGC is Benign according to our data. Variant chr1-10638911-A-AGGCCGC is described in ClinVar as [Benign]. Clinvar id is 1243264.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASZ1	NM_001079843.3	c.*30_*31insGCGGCC		3_prime_UTR_variant	21/21	ENST00000377022.8	NP_001073312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASZ1	ENST00000377022.8	c.*30_*31insGCGGCC		3_prime_UTR_variant	21/21	1	NM_001079843.3	ENSP00000366221	P1

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 9781 AN: 146246 Hom.: 565 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00771

Gnomad AMR AF: 0.0360

Gnomad ASJ AF: 0.0244

Gnomad EAS AF: 0.0591

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.0719

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.0574

GnomAD4 exome AF: 0.0434 AC: 34826 AN: 801942 Hom.: 878 Cov.: 32 AF XY: 0.0434 AC XY: 16066 AN XY: 370586

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.0422

Gnomad4 ASJ exome AF: 0.0255

Gnomad4 EAS exome AF: 0.0722

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0292

Gnomad4 NFE exome AF: 0.0393

Gnomad4 OTH exome AF: 0.0578

GnomAD4 genome AF: 0.0668 AC: 9779 AN: 146338 Hom.: 566 Cov.: 31 AF XY: 0.0655 AC XY: 4669 AN XY: 71300

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0359

Gnomad4 ASJ AF: 0.0244

Gnomad4 EAS AF: 0.0587

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0271

Gnomad4 NFE AF: 0.0341

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.00502 Hom.: 3

Asia WGS AF: 0.0520 AC: 164 AN: 3148

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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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: rs530132813; hg19: chr1-10698968;