1-10772804-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001079843.3(CASZ1):c.-233-11947G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,042 control chromosomes in the GnomAD database, including 32,918 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32918 hom., cov: 31)
• Consequence: CASZ1 NM_001079843.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASZ1	NM_001079843.3	c.-233-11947G>A		intron_variant		ENST00000377022.8
CASZ1	NM_017766.5	c.-233-11947G>A		intron_variant
CASZ1	XM_017001540.3	c.-233-11947G>A		intron_variant
CASZ1	XM_047423404.1	c.-382-11699G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASZ1	ENST00000377022.8	c.-233-11947G>A		intron_variant		1	NM_001079843.3	P1
CASZ1	ENST00000344008.5	c.-233-11947G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98219 AN: 151924 Hom.: 32916 Cov.: 31

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.645

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.646 AC: 98235 AN: 152042 Hom.: 32918 Cov.: 31 AF XY: 0.644 AC XY: 47894 AN XY: 74320

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.636

Alfa AF: 0.719 Hom.: 65958

Bravo AF: 0.634

Asia WGS AF: 0.479 AC: 1666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.32
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs205474; hg19: chr1-10832861;