rs12141589

Variant names:

• chr1-14396949-G-A
• rs12141589
• ENST00000636203.1:c.250-202034G>A

Variant summary

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

The ENST00000636203.1(KAZN):​c.250-202034G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 151,638 control chromosomes in the GnomAD database, including 511 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 0.070 (511 hom., cov: 31)
• Consequence: KAZN ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.785
• Publications: 1 publications found

Genes affected

KAZN (HGNC:29173): (kazrin, periplakin interacting protein) This gene encodes a protein that plays a role in desmosome assembly, cell adhesion, cytoskeletal organization, and epidermal differentiation. This protein co-localizes with desmoplakin and the cytolinker protein periplakin. In general, this protein localizes to the nucleus, desmosomes, cell membrane, and cortical actin-based structures. Some isoforms of this protein also associate with microtubules. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their biological validity has not been verified. [provided by RefSeq, Aug 2011]

KAZN-AS1 (HGNC:53610): (KAZN antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636203.1. 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
	KAZN-AS1	NR_149058.1		n.481-5371C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	ENST00000636203.1	TSL:5	c.250-202034G>A		intron	N/A	ENSP00000490958.1
	KAZN-AS1	ENST00000447908.3	TSL:3	n.97-5371C>T		intron	N/A
	KAZN-AS1	ENST00000657979.1		n.527-5371C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10645 AN: 151520 Hom.: 511 Cov.: 31

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.0757

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

GnomAD4 genome AF: 0.0702 AC: 10645 AN: 151638 Hom.: 511 Cov.: 31 AF XY: 0.0712 AC XY: 5273 AN XY: 74030

African (AFR) AF: 0.0154 AC: 636 AN: 41352

American (AMR) AF: 0.0484 AC: 737 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0715 AC: 248 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5156

South Asian (SAS) AF: 0.120 AC: 574 AN: 4800

European-Finnish (FIN) AF: 0.144 AC: 1496 AN: 10364

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0994 AC: 6757 AN: 67944

Other (OTH) AF: 0.0745 AC: 157 AN: 2108

Alfa AF: 0.0837 Hom.: 77

Bravo AF: 0.0584

Asia WGS AF: 0.0450 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.1
DANN	Benign	0.59
PhyloP100		0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12141589; hg19: chr1-14723445;