rs880315

Positions:

• chr1-10736809-T-C
• chr1-10736809-T-G

Variant summary

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

The NM_001079843.3(CASZ1):​c.-77+23892A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,060 control chromosomes in the GnomAD database, including 9,214 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 0.33 (9214 hom., cov: 32)
• Consequence: CASZ1 NM_001079843.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASZ1	NM_001079843.3	c.-77+23892A>G		intron_variant		ENST00000377022.8
CASZ1	NM_017766.5	c.-77+23892A>G		intron_variant
CASZ1	XM_017001540.3	c.-77+23892A>G		intron_variant
CASZ1	XM_047423404.1	c.-77+23892A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASZ1	ENST00000377022.8	c.-77+23892A>G		intron_variant		1	NM_001079843.3	P1
CASZ1	ENST00000344008.5	c.-77+23892A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50189 AN: 151942 Hom.: 9211 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.330 AC: 50202 AN: 152060 Hom.: 9214 Cov.: 32 AF XY: 0.338 AC XY: 25125 AN XY: 74332

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.322

Alfa AF: 0.352 Hom.: 22754

Bravo AF: 0.326

Asia WGS AF: 0.468 AC: 1628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.8
DANN	Benign	0.81

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: rs880315; hg19: chr1-10796866;