1-14862803-A-G

Variant names:

• chr1-14862803-A-G
• rs3845596
• NM_201628.3:c.227-97881A>G

Variant summary

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

The NM_201628.3(KAZN):​c.227-97881A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,034 control chromosomes in the GnomAD database, including 18,478 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 0.47 (18478 hom., cov: 32)
• Consequence: KAZN NM_201628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201628.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	NM_201628.3	MANE Select	c.227-97881A>G		intron	N/A	NP_963922.2
	KAZN	NM_001437721.1		c.227-97881A>G		intron	N/A	NP_001424650.1
	KAZN	NM_015209.3		c.227-97881A>G		intron	N/A	NP_056024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	ENST00000376030.7	TSL:5 MANE Select	c.227-97881A>G		intron	N/A	ENSP00000365198.2
	KAZN	ENST00000503743.5	TSL:1	c.227-97881A>G		intron	N/A	ENSP00000426015.1
	KAZN	ENST00000636203.1	TSL:5	c.491-97881A>G		intron	N/A	ENSP00000490958.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71063 AN: 151916 Hom.: 18449 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.468 AC: 71144 AN: 152034 Hom.: 18478 Cov.: 32 AF XY: 0.456 AC XY: 33905 AN XY: 74324

African (AFR) AF: 0.680 AC: 28205 AN: 41448

American (AMR) AF: 0.373 AC: 5696 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1517 AN: 3472

East Asian (EAS) AF: 0.131 AC: 675 AN: 5168

South Asian (SAS) AF: 0.339 AC: 1633 AN: 4822

European-Finnish (FIN) AF: 0.280 AC: 2967 AN: 10582

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.427 AC: 29032 AN: 67958

Other (OTH) AF: 0.492 AC: 1036 AN: 2106

Alfa AF: 0.442 Hom.: 66613

Bravo AF: 0.483

Asia WGS AF: 0.268 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.9
DANN	Benign	0.35
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3845596; hg19: chr1-15189299; COSMIC: COSV65717179;