rs516243

Positions:

• chr1-10690375-A-G

Variant summary

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

The NM_001079843.3(CASZ1):​c.16+3499T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,048 control chromosomes in the GnomAD database, including 17,156 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 0.47 (17156 hom., cov: 33)
• Consequence: CASZ1 NM_001079843.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.496

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASZ1	NM_001079843.3	c.16+3499T>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.16+3499T>C		intron_variant		1	NM_001079843.3	ENSP00000366221	P1
CASZ1	ENST00000344008.5	c.16+3499T>C		intron_variant		2		ENSP00000339445
CASZ1	ENST00000478728.2	n.39+3499T>C		intron_variant, non_coding_transcript_variant		5
CASZ1	ENST00000496432.6	n.222+3499T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70887 AN: 151930 Hom.: 17132 Cov.: 33

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.467 AC: 70938 AN: 152048 Hom.: 17156 Cov.: 33 AF XY: 0.467 AC XY: 34689 AN XY: 74314

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.479

Alfa AF: 0.490 Hom.: 29722

Bravo AF: 0.455

Asia WGS AF: 0.274 AC: 957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	11
DANN	Benign	0.34

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: rs516243; hg19: chr1-10750432;