1-10707845-C-T

Variant names:

• chr1-10707845-C-T
• rs488834
• NM_001079843.3:c.-76-2301G>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.-76-2301G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 151,962 control chromosomes in the GnomAD database, including 34,908 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 0.67 (34908 hom., cov: 31)
• Consequence: CASZ1 NM_001079843.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.03
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.754 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.-76-2301G>A		intron	N/A	NP_001073312.1	Q86V15-1
	CASZ1	NM_017766.5		c.-76-2301G>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.-76-2301G>A		intron	N/A	ENSP00000366221.3	Q86V15-1
	CASZ1	ENST00000344008.5	TSL:2	c.-76-2301G>A		intron	N/A	ENSP00000339445.5	Q86V15-2

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101277 AN: 151844 Hom.: 34913 Cov.: 31

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.667 AC: 101285 AN: 151962 Hom.: 34908 Cov.: 31 AF XY: 0.667 AC XY: 49541 AN XY: 74284

African (AFR) AF: 0.493 AC: 20397 AN: 41380

American (AMR) AF: 0.637 AC: 9730 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2847 AN: 3470

East Asian (EAS) AF: 0.556 AC: 2868 AN: 5158

South Asian (SAS) AF: 0.715 AC: 3437 AN: 4810

European-Finnish (FIN) AF: 0.760 AC: 8038 AN: 10582

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51597 AN: 67972

Other (OTH) AF: 0.694 AC: 1462 AN: 2106

Alfa AF: 0.731 Hom.: 75462

Bravo AF: 0.647

Asia WGS AF: 0.637 AC: 2215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.014
DANN	Benign	0.73
PhyloP100		-3.0
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: rs488834; hg19: chr1-10767902;