rs284277

Variant names:

• chr1-10730740-C-A
• rs284277
• NM_001079843.3:c.-76-25196G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-10730740-C-A
• chr1-10730740-C-T

Variant summary

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

The NM_001079843.3(CASZ1):​c.-76-25196G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,068 control chromosomes in the GnomAD database, including 22,390 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 0.52 (22390 hom., cov: 33)
• Consequence: CASZ1 NM_001079843.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 23 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

ENSG00000298629 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 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.-76-25196G>T		intron	N/A	NP_001073312.1	Q86V15-1
	CASZ1	NM_017766.5		c.-76-25196G>T		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.-76-25196G>T		intron	N/A	ENSP00000366221.3	Q86V15-1
	CASZ1	ENST00000344008.5	TSL:2	c.-76-25196G>T		intron	N/A	ENSP00000339445.5	Q86V15-2
	ENSG00000298629	ENST00000757011.1		n.125-944C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79553 AN: 151950 Hom.: 22389 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.523 AC: 79572 AN: 152068 Hom.: 22390 Cov.: 33 AF XY: 0.520 AC XY: 38655 AN XY: 74338

African (AFR) AF: 0.363 AC: 15076 AN: 41480

American (AMR) AF: 0.486 AC: 7424 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3472

East Asian (EAS) AF: 0.171 AC: 888 AN: 5178

South Asian (SAS) AF: 0.561 AC: 2709 AN: 4826

European-Finnish (FIN) AF: 0.587 AC: 6193 AN: 10554

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42805 AN: 67964

Other (OTH) AF: 0.554 AC: 1169 AN: 2112

Alfa AF: 0.593 Hom.: 106630

Bravo AF: 0.507

Asia WGS AF: 0.361 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.62
PhyloP100		0.13
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: rs284277; hg19: chr1-10790797; COSMIC: COSV59733874;