rs2480054

Positions:

• chr1-14466039-A-G
• chr1-14466039-A-T

Variant summary

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

The ENST00000636203.1(KAZN):​c.250-132944A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,986 control chromosomes in the GnomAD database, including 23,591 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 0.55 (23591 hom., cov: 32)
• Consequence: KAZN ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAZN	XM_005245795.6	c.280-132944A>G		intron_variant			XP_005245852.1
KAZN	XM_011541074.4	c.280-132944A>G		intron_variant			XP_011539376.1
KAZN	XM_011541080.4	c.280-132944A>G		intron_variant			XP_011539382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAZN	ENST00000636203.1	c.250-132944A>G		intron_variant		5		ENSP00000490958	A2

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84236 AN: 151868 Hom.: 23581 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.555 AC: 84286 AN: 151986 Hom.: 23591 Cov.: 32 AF XY: 0.557 AC XY: 41400 AN XY: 74302

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.549

Alfa AF: 0.566 Hom.: 24398

Bravo AF: 0.551

Asia WGS AF: 0.635 AC: 2206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2480054; hg19: chr1-14792535;