rs284320

chr1-10666963-T-C

Variant summary

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

The NM_001079843.3(CASZ1):c.17-1392A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,128 control chromosomes in the GnomAD database, including 7,045 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 0.28 (7045 hom., cov: 33)
• Consequence: CASZ1 NM_001079843.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASZ1	NM_001079843.3	c.17-1392A>G		intron_variant		ENST00000377022.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASZ1	ENST00000377022.8	c.17-1392A>G		intron_variant		1	NM_001079843.3	P1
CASZ1	ENST00000344008.5	c.17-1392A>G		intron_variant		2
CASZ1	ENST00000478728.2	n.40-1392A>G		intron_variant, non_coding_transcript_variant		5
CASZ1	ENST00000496432.6	n.223-1392A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43000 AN: 152008 Hom.: 7010 Cov.: 33

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.283 AC: 43083 AN: 152128 Hom.: 7045 Cov.: 33 AF XY: 0.287 AC XY: 21327 AN XY: 74372

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.264

Alfa AF: 0.236 Hom.: 1268

Bravo AF: 0.283

Asia WGS AF: 0.257 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.7
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs284320; hg19: chr1-10727020;