rs284277

chr1-10730740-C-Achr1-10730740-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.-76-25196G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,068 control chromosomes in the GnomAD database, including 22,390 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 0.52 (22390 hom., cov: 33)
• Consequence: CASZ1 NM_001079843.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASZ1	NM_001079843.3	c.-76-25196G>T		intron_variant		ENST00000377022.8
CASZ1	NM_017766.5	c.-76-25196G>T		intron_variant
CASZ1	XM_017001540.3	c.-76-25196G>T		intron_variant
CASZ1	XM_047423404.1	c.-76-25196G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASZ1	ENST00000377022.8	c.-76-25196G>T		intron_variant		1	NM_001079843.3	P1
CASZ1	ENST00000344008.5	c.-76-25196G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79553 AN: 151950 Hom.: 22389 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.523 AC: 79572 AN: 152068 Hom.: 22390 Cov.: 33 AF XY: 0.520 AC XY: 38655 AN XY: 74338

Gnomad4 AFR AF: 0.363

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.554

Alfa AF: 0.608 Hom.: 47963

Bravo AF: 0.507

Asia WGS AF: 0.361 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.8
Dann	Benign	0.62

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: rs284277; hg19: chr1-10790797; COSMIC: COSV59733874;