NM_001079843.3:c.17-1392A>G

Variant names:

• chr1-10666963-T-C
• rs284320
• NM_001079843.3:c.17-1392A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

CASZ1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079843.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASZ1	NM_001079843.3	MANE Select	c.17-1392A>G		intron	N/A	NP_001073312.1	Q86V15-1
	CASZ1	NM_017766.5		c.17-1392A>G		intron	N/A	NP_060236.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASZ1	ENST00000377022.8	TSL:1 MANE Select	c.17-1392A>G		intron	N/A	ENSP00000366221.3	Q86V15-1
	CASZ1	ENST00000344008.5	TSL:2	c.17-1392A>G		intron	N/A	ENSP00000339445.5	Q86V15-2
	CASZ1	ENST00000478728.2	TSL:5	n.40-1392A>G		intron	N/A

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

African (AFR) AF: 0.440 AC: 18274 AN: 41486

American (AMR) AF: 0.233 AC: 3569 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 895 AN: 3468

East Asian (EAS) AF: 0.191 AC: 987 AN: 5168

South Asian (SAS) AF: 0.311 AC: 1499 AN: 4824

European-Finnish (FIN) AF: 0.306 AC: 3247 AN: 10594

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13737 AN: 67974

Other (OTH) AF: 0.264 AC: 558 AN: 2114

Alfa AF: 0.240 Hom.: 1343

Bravo AF: 0.283

Asia WGS AF: 0.257 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.61
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs284320; hg19: chr1-10727020;