1-14543230-C-T

Position:

• chr1-14543230-C-T

Variant summary

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

The ENST00000636203.1(KAZN):​c.250-55753C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,092 control chromosomes in the GnomAD database, including 13,793 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 0.42 (13793 hom., cov: 32)
• Consequence: KAZN ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619

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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAZN	XM_011541074.4	c.280-55753C>T		intron_variant			XP_011539376.1
KAZN	XM_005245795.6	c.280-55753C>T		intron_variant			XP_005245852.1
KAZN	XM_011541080.4	c.280-55753C>T		intron_variant			XP_011539382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAZN	ENST00000636203.1	c.250-55753C>T		intron_variant		5		ENSP00000490958.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63187 AN: 151976 Hom.: 13789 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.416 AC: 63205 AN: 152092 Hom.: 13793 Cov.: 32 AF XY: 0.411 AC XY: 30594 AN XY: 74354

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.438

Alfa AF: 0.312 Hom.: 795

Bravo AF: 0.406

Asia WGS AF: 0.424 AC: 1473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3927648; hg19: chr1-14869726;