1-10772804-C-T

Variant names:

• chr1-10772804-C-T
• rs205474
• NM_001079843.3:c.-233-11947G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001079843.3(CASZ1):​c.-233-11947G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,042 control chromosomes in the GnomAD database, including 32,918 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 0.65 (32918 hom., cov: 31)
• Consequence: CASZ1 NM_001079843.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.735 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.-233-11947G>A		intron	N/A	NP_001073312.1	Q86V15-1
	CASZ1	NM_017766.5		c.-233-11947G>A		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.-233-11947G>A		intron	N/A	ENSP00000366221.3	Q86V15-1
	CASZ1	ENST00000344008.5	TSL:2	c.-233-11947G>A		intron	N/A	ENSP00000339445.5	Q86V15-2

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98219 AN: 151924 Hom.: 32916 Cov.: 31

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.646 AC: 98235 AN: 152042 Hom.: 32918 Cov.: 31 AF XY: 0.644 AC XY: 47894 AN XY: 74320

African (AFR) AF: 0.482 AC: 19990 AN: 41442

American (AMR) AF: 0.645 AC: 9860 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2604 AN: 3472

East Asian (EAS) AF: 0.436 AC: 2250 AN: 5158

South Asian (SAS) AF: 0.592 AC: 2845 AN: 4806

European-Finnish (FIN) AF: 0.766 AC: 8106 AN: 10588

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.740 AC: 50308 AN: 67974

Other (OTH) AF: 0.636 AC: 1345 AN: 2114

Alfa AF: 0.709 Hom.: 143357

Bravo AF: 0.634

Asia WGS AF: 0.479 AC: 1666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.32
DANN	Benign	0.60
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs205474; hg19: chr1-10832861;