ENST00000636203.1:c.92-19222G>A

Variant names:

• chr1-14161213-G-A
• rs1416633
• ENST00000636203.1:c.92-19222G>A

Variant summary

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

The ENST00000636203.1(KAZN):​c.92-19222G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,208 control chromosomes in the GnomAD database, including 3,479 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 0.19 (3479 hom., cov: 33)
• Consequence: KAZN ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 2 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.329 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	ENST00000636203.1	TSL:5	c.92-19222G>A		intron	N/A	ENSP00000490958.1
	KAZN	ENST00000636564.1	TSL:5	c.92-19222G>A		intron	N/A	ENSP00000489835.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29249 AN: 152090 Hom.: 3477 Cov.: 33

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.0221

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.192 AC: 29252 AN: 152208 Hom.: 3479 Cov.: 33 AF XY: 0.197 AC XY: 14681 AN XY: 74422

African (AFR) AF: 0.0779 AC: 3237 AN: 41544

American (AMR) AF: 0.165 AC: 2527 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3468

East Asian (EAS) AF: 0.0212 AC: 110 AN: 5188

South Asian (SAS) AF: 0.343 AC: 1653 AN: 4824

European-Finnish (FIN) AF: 0.314 AC: 3317 AN: 10580

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16754 AN: 67992

Other (OTH) AF: 0.188 AC: 398 AN: 2116

Alfa AF: 0.216 Hom.: 5670

Bravo AF: 0.172

Asia WGS AF: 0.184 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.4
DANN	Benign	0.53
PhyloP100		0.096

Splicing

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

Other links and lift over

dbSNP: rs1416633; hg19: chr1-14487708;