ENST00000636203.1:c.250-176719G>A

Variant names:

• chr1-14422264-G-A
• rs7531416
• ENST00000636203.1:c.250-176719G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KAZN	XM_011541074.4	c.280-176719G>A		intron_variant	Intron 2 of 15		XP_011539376.1
KAZN	XM_005245795.6	c.280-176719G>A		intron_variant	Intron 2 of 16		XP_005245852.1
KAZN	XM_011541080.4	c.280-176719G>A		intron_variant	Intron 2 of 12		XP_011539382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAZN	ENST00000636203.1	c.250-176719G>A		intron_variant	Intron 2 of 16	5		ENSP00000490958.1

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

African (AFR) AF: 0.564 AC: 23387 AN: 41456

American (AMR) AF: 0.349 AC: 5323 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1527 AN: 3470

East Asian (EAS) AF: 0.338 AC: 1745 AN: 5170

South Asian (SAS) AF: 0.209 AC: 1007 AN: 4828

European-Finnish (FIN) AF: 0.345 AC: 3644 AN: 10552

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29804 AN: 67964

Other (OTH) AF: 0.451 AC: 951 AN: 2108

Alfa AF: 0.406 Hom.: 4413

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
PhyloP100		-0.097

Splicing

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

Other links and lift over

dbSNP: rs7531416; hg19: chr1-14748760;