rs6667220

Variant names:

• chr1-15021144-G-A
• rs6667220
• NM_201628.3:c.419-13605G>A

Variant summary

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

The NM_201628.3(KAZN):​c.419-13605G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 151,978 control chromosomes in the GnomAD database, including 41,977 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 0.74 (41977 hom., cov: 31)
• Consequence: KAZN NM_201628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.805 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	NM_201628.3	MANE Select	c.419-13605G>A		intron	N/A	NP_963922.2	Q674X7-1
	KAZN	NM_001437721.1		c.419-13605G>A		intron	N/A	NP_001424650.1
	KAZN	NM_015209.3		c.419-13605G>A		intron	N/A	NP_056024.1	Q674X7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	ENST00000376030.7	TSL:5 MANE Select	c.419-13605G>A		intron	N/A	ENSP00000365198.2	Q674X7-1
	KAZN	ENST00000503743.5	TSL:1	c.419-13605G>A		intron	N/A	ENSP00000426015.1	Q674X7-2
	KAZN	ENST00000361144.9	TSL:1	c.401-13605G>A		intron	N/A	ENSP00000354727.5	Q674X7-3

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112546 AN: 151860 Hom.: 41941 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.748

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

GnomAD4 genome AF: 0.741 AC: 112645 AN: 151978 Hom.: 41977 Cov.: 31 AF XY: 0.739 AC XY: 54846 AN XY: 74266

African (AFR) AF: 0.762 AC: 31585 AN: 41438

American (AMR) AF: 0.817 AC: 12477 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2489 AN: 3470

East Asian (EAS) AF: 0.497 AC: 2565 AN: 5156

South Asian (SAS) AF: 0.711 AC: 3421 AN: 4814

European-Finnish (FIN) AF: 0.728 AC: 7687 AN: 10552

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 49997 AN: 67958

Other (OTH) AF: 0.744 AC: 1566 AN: 2106

Alfa AF: 0.734 Hom.: 178981

Bravo AF: 0.750

Asia WGS AF: 0.587 AC: 2040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.048
DANN	Benign	0.93
PhyloP100		-1.5
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: rs6667220; hg19: chr1-15347640;