rs12046278

Variant names:

• chr1-10739520-T-C
• rs12046278
• NM_001079843.3:c.-77+21181A>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.-77+21181A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,030 control chromosomes in the GnomAD database, including 11,037 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 0.37 (11037 hom., cov: 32)
• Consequence: CASZ1 NM_001079843.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 32 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASZ1	NM_001079843.3	c.-77+21181A>G		intron_variant	Intron 2 of 20	ENST00000377022.8	NP_001073312.1
CASZ1	NM_017766.5	c.-77+21181A>G		intron_variant	Intron 2 of 15		NP_060236.3
CASZ1	XM_017001540.3	c.-77+21181A>G		intron_variant	Intron 2 of 21		XP_016857029.1
CASZ1	XM_047423404.1	c.-77+21181A>G		intron_variant	Intron 3 of 22		XP_047279360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASZ1	ENST00000377022.8	c.-77+21181A>G		intron_variant	Intron 2 of 20	1	NM_001079843.3	ENSP00000366221.3
CASZ1	ENST00000344008.5	c.-77+21181A>G		intron_variant	Intron 2 of 15	2		ENSP00000339445.5

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55932 AN: 151912 Hom.: 11028 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.368 AC: 55967 AN: 152030 Hom.: 11037 Cov.: 32 AF XY: 0.376 AC XY: 27956 AN XY: 74312

African (AFR) AF: 0.286 AC: 11876 AN: 41462

American (AMR) AF: 0.487 AC: 7449 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 880 AN: 3472

East Asian (EAS) AF: 0.720 AC: 3710 AN: 5156

South Asian (SAS) AF: 0.433 AC: 2086 AN: 4822

European-Finnish (FIN) AF: 0.432 AC: 4569 AN: 10588

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24236 AN: 67924

Other (OTH) AF: 0.360 AC: 760 AN: 2110

Alfa AF: 0.365 Hom.: 23869

Bravo AF: 0.368

Asia WGS AF: 0.537 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.49
PhyloP100		0.049
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: rs12046278; hg19: chr1-10799577;