rs284251

Positions:

• chr1-10641567-C-G
• chr1-10641567-C-T

Variant summary

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

The ENST00000377022.8(CASZ1):​c.4162+1292G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,180 control chromosomes in the GnomAD database, including 5,306 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 0.24 (5306 hom., cov: 33)
• Consequence: CASZ1 ENST00000377022.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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]

(HGNC:):

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 = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASZ1	NM_001079843.3	c.4162+1292G>C		intron_variant		ENST00000377022.8	NP_001073312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASZ1	ENST00000377022.8	c.4162+1292G>C		intron_variant		1	NM_001079843.3	ENSP00000366221	P1
	ENST00000606802.1	n.837+1490C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36931 AN: 152060 Hom.: 5274 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.243 AC: 37010 AN: 152180 Hom.: 5306 Cov.: 33 AF XY: 0.247 AC XY: 18391 AN XY: 74416

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.229

Alfa AF: 0.211 Hom.: 505

Bravo AF: 0.243

Asia WGS AF: 0.177 AC: 618 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	2.3
DANN	Benign	0.53

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: rs284251; hg19: chr1-10701624;