rs4128690

Variant names:

• chr1-14418385-C-T
• rs4128690
• ENST00000636203.1:c.250-180598C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636203.1(KAZN):​c.250-180598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,958 control chromosomes in the GnomAD database, including 15,078 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 (15078 hom., cov: 32)
• Consequence: KAZN ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 2 publications found

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]

KAZN-AS1 (HGNC:53610): (KAZN antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAZN-AS1	NR_149058.1	n.480+1109G>A		intron_variant	Intron 1 of 4
KAZN	XM_011541074.4	c.280-180598C>T		intron_variant	Intron 2 of 15		XP_011539376.1
KAZN	XM_005245795.6	c.280-180598C>T		intron_variant	Intron 2 of 16		XP_005245852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAZN	ENST00000636203.1	c.250-180598C>T		intron_variant	Intron 2 of 16	5		ENSP00000490958.1
KAZN-AS1	ENST00000447908.3	n.96+1109G>A		intron_variant	Intron 1 of 4	3
KAZN-AS1	ENST00000657979.1	n.480+1109G>A		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66555 AN: 151840 Hom.: 15065 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.438 AC: 66611 AN: 151958 Hom.: 15078 Cov.: 32 AF XY: 0.427 AC XY: 31678 AN XY: 74256

African (AFR) AF: 0.524 AC: 21696 AN: 41428

American (AMR) AF: 0.348 AC: 5302 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1563 AN: 3470

East Asian (EAS) AF: 0.331 AC: 1707 AN: 5164

South Asian (SAS) AF: 0.205 AC: 990 AN: 4822

European-Finnish (FIN) AF: 0.346 AC: 3648 AN: 10554

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30101 AN: 67958

Other (OTH) AF: 0.448 AC: 946 AN: 2110

Alfa AF: 0.427 Hom.: 7160

Bravo AF: 0.448

Asia WGS AF: 0.282 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.037
DANN	Benign	0.43
PhyloP100		-2.5

Splicing

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

Other links and lift over

dbSNP: rs4128690; hg19: chr1-14744881;