1-14416227-T-C

Variant summary

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

The NR_149058.1(KAZN-AS1):n.480+3267A>G 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 0.917 in 152,224 control chromosomes in the GnomAD database, including 64,036 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 0.92 (64036 hom., cov: 31)
• Consequence: KAZN-AS1 NR_149058.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAZN-AS1	NR_149058.1	n.480+3267A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAZN-AS1	ENST00000666654.1	n.480+3267A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.917 AC: 139417 AN: 152106 Hom.: 63990 Cov.: 31

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.917 AC: 139522 AN: 152224 Hom.: 64036 Cov.: 31 AF XY: 0.917 AC XY: 68208 AN XY: 74422

Gnomad4 AFR AF: 0.942

Gnomad4 AMR AF: 0.869

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.869

Gnomad4 FIN AF: 0.947

Gnomad4 NFE AF: 0.908

Gnomad4 OTH AF: 0.895

Alfa AF: 0.901 Hom.: 61432

Bravo AF: 0.913

Asia WGS AF: 0.912 AC: 3171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	12
Dann	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10754855; hg19: chr1-14742723;