rs2105239

Positions:

• chr1-14531147-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636203.1(KAZN):​c.250-67836A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,046 control chromosomes in the GnomAD database, including 15,158 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 0.44 (15158 hom., cov: 32)
• Consequence: KAZN ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAZN	XM_005245795.6	c.280-67836A>G		intron_variant			XP_005245852.1
KAZN	XM_011541074.4	c.280-67836A>G		intron_variant			XP_011539376.1
KAZN	XM_011541080.4	c.280-67836A>G		intron_variant			XP_011539382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAZN	ENST00000636203.1	c.250-67836A>G		intron_variant		5		ENSP00000490958	A2

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66673 AN: 151926 Hom.: 15160 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.439 AC: 66685 AN: 152046 Hom.: 15158 Cov.: 32 AF XY: 0.435 AC XY: 32338 AN XY: 74342

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.469

Alfa AF: 0.501 Hom.: 32343

Bravo AF: 0.431

Asia WGS AF: 0.448 AC: 1559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2105239; hg19: chr1-14857643;