1-14683324-T-C

Position:

• chr1-14683324-T-C

Variant summary

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

The NM_201628.3(KAZN):​c.226+84101T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,018 control chromosomes in the GnomAD database, including 21,713 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 0.53 (21713 hom., cov: 32)
• Consequence: KAZN NM_201628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639

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 (SAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAZN	NM_201628.3	c.226+84101T>C		intron_variant		ENST00000376030.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAZN	ENST00000376030.7	c.226+84101T>C		intron_variant		5	NM_201628.3	P2
KAZN	ENST00000503743.5	c.226+84101T>C		intron_variant		1
KAZN	ENST00000636203.1	c.490+84101T>C		intron_variant		5		A2
KAZN	ENST00000491547.1	n.520+84101T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81035 AN: 151896 Hom.: 21689 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.534 AC: 81108 AN: 152018 Hom.: 21713 Cov.: 32 AF XY: 0.533 AC XY: 39583 AN XY: 74292

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.508

Alfa AF: 0.470 Hom.: 2707

Bravo AF: 0.521

Asia WGS AF: 0.574 AC: 1997 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	0.65
DANN	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1883661; hg19: chr1-15009820; COSMIC: COSV65716616;