rs12046278

chr1-10739520-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.-77+21181A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,030 control chromosomes in the GnomAD database, including 11,037 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 0.37 (11037 hom., cov: 32)
• Consequence: CASZ1 NM_001079843.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASZ1	NM_001079843.3	c.-77+21181A>G		intron_variant		ENST00000377022.8
CASZ1	NM_017766.5	c.-77+21181A>G		intron_variant
CASZ1	XM_017001540.3	c.-77+21181A>G		intron_variant
CASZ1	XM_047423404.1	c.-77+21181A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASZ1	ENST00000377022.8	c.-77+21181A>G		intron_variant		1	NM_001079843.3	P1
CASZ1	ENST00000344008.5	c.-77+21181A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55932 AN: 151912 Hom.: 11028 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.368 AC: 55967 AN: 152030 Hom.: 11037 Cov.: 32 AF XY: 0.376 AC XY: 27956 AN XY: 74312

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.360

Alfa AF: 0.368 Hom.: 14832

Bravo AF: 0.368

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.6
Dann	Benign	0.49

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: rs12046278; hg19: chr1-10799577;