1-14044642-T-G

Variant names:

• chr1-14044642-T-G
• rs761162
• ENST00000636203.1:c.92-135793T>G

Variant summary

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

The ENST00000636203.1(KAZN):​c.92-135793T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 151,818 control chromosomes in the GnomAD database, including 30,229 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 0.62 (30229 hom., cov: 31)
• Consequence: KAZN ENST00000636203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAZN	XM_011541074.4	c.122-135793T>G		intron_variant	Intron 1 of 15		XP_011539376.1
KAZN	XM_005245795.6	c.122-135793T>G		intron_variant	Intron 1 of 16		XP_005245852.1
KAZN	XM_011541080.4	c.122-135793T>G		intron_variant	Intron 1 of 12		XP_011539382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAZN	ENST00000636203.1	c.92-135793T>G		intron_variant	Intron 1 of 16	5		ENSP00000490958.1
KAZN	ENST00000636564.1	c.92-135793T>G		intron_variant	Intron 1 of 2	5		ENSP00000489835.1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93529 AN: 151700 Hom.: 30185 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.617 AC: 93622 AN: 151818 Hom.: 30229 Cov.: 31 AF XY: 0.620 AC XY: 45991 AN XY: 74182

African (AFR) AF: 0.801 AC: 33155 AN: 41404

American (AMR) AF: 0.703 AC: 10740 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1926 AN: 3470

East Asian (EAS) AF: 0.702 AC: 3623 AN: 5162

South Asian (SAS) AF: 0.530 AC: 2541 AN: 4792

European-Finnish (FIN) AF: 0.557 AC: 5866 AN: 10528

Middle Eastern (MID) AF: 0.514 AC: 150 AN: 292

European-Non Finnish (NFE) AF: 0.500 AC: 33931 AN: 67880

Other (OTH) AF: 0.626 AC: 1320 AN: 2108

Alfa AF: 0.527 Hom.: 11162

Bravo AF: 0.638

Asia WGS AF: 0.640 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.53
PhyloP100		-0.25

Splicing

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

Other links and lift over

dbSNP: rs761162; hg19: chr1-14371137;