1-14417476-A-G

Variant names:

• chr1-14417476-A-G
• rs4573512
• ENST00000636203.1:c.250-181507A>G

Variant summary

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

The ENST00000447908.3(KAZN-AS1):​n.96+2018T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,000 control chromosomes in the GnomAD database, including 14,428 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 0.43 (14428 hom., cov: 31)
• Consequence: KAZN-AS1 ENST00000447908.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 3 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=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000447908.3. 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-AS1	NR_149058.1		n.480+2018T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZN	ENST00000636203.1	TSL:5	c.250-181507A>G		intron	N/A	ENSP00000490958.1	A0A1B0GWK2
	KAZN-AS1	ENST00000447908.3	TSL:3	n.96+2018T>C		intron	N/A
	KAZN-AS1	ENST00000657979.1		n.480+2018T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65273 AN: 151882 Hom.: 14422 Cov.: 31

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.430 AC: 65315 AN: 152000 Hom.: 14428 Cov.: 31 AF XY: 0.418 AC XY: 31067 AN XY: 74302

African (AFR) AF: 0.490 AC: 20321 AN: 41434

American (AMR) AF: 0.346 AC: 5283 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1564 AN: 3472

East Asian (EAS) AF: 0.341 AC: 1755 AN: 5144

South Asian (SAS) AF: 0.210 AC: 1012 AN: 4822

European-Finnish (FIN) AF: 0.345 AC: 3656 AN: 10584

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

European-Non Finnish (NFE) AF: 0.443 AC: 30135 AN: 67954

Other (OTH) AF: 0.442 AC: 931 AN: 2108

Alfa AF: 0.427 Hom.: 23738

Bravo AF: 0.439

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.4
DANN	Benign	0.84
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs4573512; hg19: chr1-14743972;