rs4128690

Positions:

• chr1-14418385-C-T

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+1109G>A 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 0.438 in 151,958 control chromosomes in the GnomAD database, including 15,078 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 0.44 (15078 hom., cov: 32)
• Consequence: KAZN-AS1 NR_149058.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAZN-AS1	NR_149058.1	n.480+1109G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAZN-AS1	ENST00000666654.1	n.480+1109G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66555 AN: 151840 Hom.: 15065 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.438 AC: 66611 AN: 151958 Hom.: 15078 Cov.: 32 AF XY: 0.427 AC XY: 31678 AN XY: 74256

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.448

Alfa AF: 0.424 Hom.: 6283

Bravo AF: 0.448

Asia WGS AF: 0.282 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.037
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4128690; hg19: chr1-14744881;