rs12141589

Positions:

• chr1-14396949-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_149058.1(KAZN-AS1):​n.481-5371C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 151,638 control chromosomes in the GnomAD database, including 511 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 0.070 (511 hom., cov: 31)
• Consequence: KAZN-AS1 NR_149058.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.785

Genes affected

KAZN-AS1 (HGNC:53610): (KAZN antisense RNA 1)

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAZN-AS1	NR_149058.1	n.481-5371C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAZN-AS1	ENST00000666654.1	n.481-5371C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10645 AN: 151520 Hom.: 511 Cov.: 31

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.0757

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

GnomAD4 genome AF: 0.0702 AC: 10645 AN: 151638 Hom.: 511 Cov.: 31 AF XY: 0.0712 AC XY: 5273 AN XY: 74030

Gnomad4 AFR AF: 0.0154

Gnomad4 AMR AF: 0.0484

Gnomad4 ASJ AF: 0.0715

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0994

Gnomad4 OTH AF: 0.0745

Alfa AF: 0.0837 Hom.: 77

Bravo AF: 0.0584

Asia WGS AF: 0.0450 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.1
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12141589; hg19: chr1-14723445;