NM_001079843.3:c.16+3499T>C

Variant names:

• chr1-10690375-A-G
• rs516243
• NM_001079843.3:c.16+3499T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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]

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 = 0.491 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASZ1	NM_001079843.3	MANE Select	c.16+3499T>C		intron	N/A	NP_001073312.1
	CASZ1	NM_017766.5		c.16+3499T>C		intron	N/A	NP_060236.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASZ1	ENST00000377022.8	TSL:1 MANE Select	c.16+3499T>C		intron	N/A	ENSP00000366221.3
	CASZ1	ENST00000344008.5	TSL:2	c.16+3499T>C		intron	N/A	ENSP00000339445.5
	CASZ1	ENST00000478728.2	TSL:5	n.39+3499T>C		intron	N/A

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

African (AFR) AF: 0.448 AC: 18589 AN: 41464

American (AMR) AF: 0.418 AC: 6391 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2034 AN: 3470

East Asian (EAS) AF: 0.160 AC: 826 AN: 5170

South Asian (SAS) AF: 0.400 AC: 1929 AN: 4822

European-Finnish (FIN) AF: 0.547 AC: 5786 AN: 10570

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.495 AC: 33648 AN: 67962

Other (OTH) AF: 0.479 AC: 1014 AN: 2116

Alfa AF: 0.483 Hom.: 52561

Bravo AF: 0.455

Asia WGS AF: 0.274 AC: 957 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	11
DANN	Benign	0.34
PhyloP100		0.50
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: rs516243; hg19: chr1-10750432;