1-13916277-C-T

Variant names:

• chr1-13916277-C-T
• rs16853148
• ENST00000636203.1:c.91+22521C>T

Variant summary

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

The ENST00000636203.1(KAZN):​c.91+22521C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 152,152 control chromosomes in the GnomAD database, including 485 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 0.073 (485 hom., cov: 32)
• Consequence: KAZN ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	ENST00000636203.1	TSL:5	c.91+22521C>T		intron	N/A	ENSP00000490958.1	A0A1B0GWK2
	KAZN	ENST00000636564.1	TSL:5	c.91+22521C>T		intron	N/A	ENSP00000489835.1	A0A1B0GTU0

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11120 AN: 152034 Hom.: 484 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0617

Gnomad OTH AF: 0.0532

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

GnomAD4 genome AF: 0.0732 AC: 11135 AN: 152152 Hom.: 485 Cov.: 32 AF XY: 0.0717 AC XY: 5331 AN XY: 74394

African (AFR) AF: 0.106 AC: 4415 AN: 41490

American (AMR) AF: 0.0337 AC: 515 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0406 AC: 141 AN: 3470

East Asian (EAS) AF: 0.139 AC: 718 AN: 5168

South Asian (SAS) AF: 0.0860 AC: 414 AN: 4816

European-Finnish (FIN) AF: 0.0562 AC: 596 AN: 10604

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0617 AC: 4195 AN: 67994

Other (OTH) AF: 0.0564 AC: 119 AN: 2110

Alfa AF: 0.0577 Hom.: 492

Bravo AF: 0.0717

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.1
DANN	Benign	0.65
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs16853148; hg19: chr1-14242772;