1-14416227-T-C

Variant names:

• chr1-14416227-T-C
• rs10754855
• ENST00000636203.1:c.250-182756T>C

Variant summary

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

The ENST00000636203.1(KAZN):​c.250-182756T>C variant causes a intron 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 ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 6 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=-0.88).
• 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 rank	MANE	Protein	UniProt
KAZN-AS1	NR_149058.1	n.480+3267A>G		intron_variant	Intron 1 of 4
KAZN	XM_011541074.4	c.280-182756T>C		intron_variant	Intron 2 of 15		XP_011539376.1
KAZN	XM_005245795.6	c.280-182756T>C		intron_variant	Intron 2 of 16		XP_005245852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAZN	ENST00000636203.1	c.250-182756T>C		intron_variant	Intron 2 of 16	5		ENSP00000490958.1
KAZN-AS1	ENST00000447908.3	n.96+3267A>G		intron_variant	Intron 1 of 4	3
KAZN-AS1	ENST00000657979.1	n.480+3267A>G		intron_variant	Intron 1 of 5

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

African (AFR) AF: 0.942 AC: 39139 AN: 41528

American (AMR) AF: 0.869 AC: 13301 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3159 AN: 3472

East Asian (EAS) AF: 0.953 AC: 4932 AN: 5176

South Asian (SAS) AF: 0.869 AC: 4187 AN: 4816

European-Finnish (FIN) AF: 0.947 AC: 10043 AN: 10602

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61752 AN: 68010

Other (OTH) AF: 0.895 AC: 1894 AN: 2116

Alfa AF: 0.903 Hom.: 80363

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
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs10754855; hg19: chr1-14742723;