1-14340098-A-ATCACAGAC

Variant names:

• chr1-14340098-A-ATCACAGAC
• rs2308043
• ENST00000636203.1:c.249+159506_249+159507insTCACAGAC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000636203.1(KAZN):​c.249+159506_249+159507insTCACAGAC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (13163 hom., cov: 0)
• Consequence: KAZN ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 2 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAZN	XM_011541074.4	c.279+159508_279+159509insACAGACTC		intron_variant	Intron 2 of 15		XP_011539376.1
KAZN	XM_005245795.6	c.279+159508_279+159509insACAGACTC		intron_variant	Intron 2 of 16		XP_005245852.1
KAZN	XM_011541080.4	c.279+159508_279+159509insACAGACTC		intron_variant	Intron 2 of 12		XP_011539382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAZN	ENST00000636203.1	c.249+159506_249+159507insTCACAGAC		intron_variant	Intron 2 of 16	5		ENSP00000490958.1
KAZN-AS1	ENST00000666654.1	n.1150-1081_1150-1080insGTCTGTGA		intron_variant	Intron 6 of 6

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59939 AN: 151880 Hom.: 13129 Cov.: 0

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.395 AC: 60009 AN: 151996 Hom.: 13163 Cov.: 0 AF XY: 0.392 AC XY: 29116 AN XY: 74280

African (AFR) AF: 0.591 AC: 24461 AN: 41408

American (AMR) AF: 0.254 AC: 3881 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 889 AN: 3472

East Asian (EAS) AF: 0.383 AC: 1981 AN: 5166

South Asian (SAS) AF: 0.412 AC: 1983 AN: 4814

European-Finnish (FIN) AF: 0.314 AC: 3309 AN: 10554

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22406 AN: 67984

Other (OTH) AF: 0.341 AC: 718 AN: 2108

Alfa AF: 0.170 Hom.: 283

Bravo AF: 0.392

Asia WGS AF: 0.370 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs2308043; hg19: chr1-14666593;