rs7531416

chr1-14422264-G-Achr1-14422264-G-T

Variant summary

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

The ENST00000636203.1(KAZN):c.250-176719G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,022 control chromosomes in the GnomAD database, including 15,890 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 0.45 (15890 hom., cov: 33)
• Consequence: KAZN ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAZN	XM_005245795.6	c.280-176719G>A		intron_variant
KAZN	XM_011541074.4	c.280-176719G>A		intron_variant
KAZN	XM_011541080.4	c.280-176719G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAZN	ENST00000636203.1	c.250-176719G>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67938 AN: 151904 Hom.: 15869 Cov.: 33

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.447 AC: 68002 AN: 152022 Hom.: 15890 Cov.: 33 AF XY: 0.436 AC XY: 32363 AN XY: 74282

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.451

Alfa AF: 0.375 Hom.: 1932

Bravo AF: 0.459

Asia WGS AF: 0.291 AC: 1012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.85
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7531416; hg19: chr1-14748760;