rs7515649

Variant names:

• chr1-15106368-C-A
• rs7515649
• NM_201628.3:c.2048+2179C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-15106368-C-A
• chr1-15106368-C-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.2048+2179C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,120 control chromosomes in the GnomAD database, including 3,271 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 0.20 (3271 hom., cov: 32)
• Consequence: KAZN NM_201628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 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.2048+2179C>A		intron	N/A	NP_963922.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	ENST00000376030.7	TSL:5 MANE Select	c.2048+2179C>A		intron	N/A	ENSP00000365198.2
	KAZN	ENST00000636203.1	TSL:5	c.2312+2179C>A		intron	N/A	ENSP00000490958.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30671 AN: 152004 Hom.: 3270 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.202 AC: 30692 AN: 152120 Hom.: 3271 Cov.: 32 AF XY: 0.199 AC XY: 14818 AN XY: 74350

African (AFR) AF: 0.253 AC: 10511 AN: 41482

American (AMR) AF: 0.140 AC: 2141 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3466

East Asian (EAS) AF: 0.0500 AC: 259 AN: 5176

South Asian (SAS) AF: 0.152 AC: 734 AN: 4814

European-Finnish (FIN) AF: 0.195 AC: 2067 AN: 10584

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13382 AN: 67994

Other (OTH) AF: 0.197 AC: 417 AN: 2112

Alfa AF: 0.199 Hom.: 1156

Bravo AF: 0.201

Asia WGS AF: 0.121 AC: 420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.76
DANN	Benign	0.42
PhyloP100		-0.94
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: rs7515649; hg19: chr1-15432864;