chr1-14754064-C-A

Variant names:

• chr1-14754064-C-A
• rs4357518
• NM_201628.3:c.226+154841C>A

Variant summary

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

The NM_201628.3(KAZN):​c.226+154841C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,042 control chromosomes in the GnomAD database, including 15,899 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 0.45 (15899 hom., cov: 32)
• Consequence: KAZN NM_201628.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAZN	NM_201628.3	c.226+154841C>A		intron_variant	Intron 1 of 14	ENST00000376030.7	NP_963922.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAZN	ENST00000376030.7	c.226+154841C>A		intron_variant	Intron 1 of 14	5	NM_201628.3	ENSP00000365198.2
KAZN	ENST00000503743.5	c.226+154841C>A		intron_variant	Intron 2 of 8	1		ENSP00000426015.1
KAZN	ENST00000636203.1	c.490+154841C>A		intron_variant	Intron 3 of 16	5		ENSP00000490958.1
KAZN	ENST00000491547.1	n.520+154841C>A		intron_variant	Intron 1 of 6	2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67981 AN: 151924 Hom.: 15903 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.447 AC: 67986 AN: 152042 Hom.: 15899 Cov.: 32 AF XY: 0.443 AC XY: 32922 AN XY: 74298

African (AFR) AF: 0.380 AC: 15741 AN: 41464

American (AMR) AF: 0.376 AC: 5755 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 2001 AN: 3472

East Asian (EAS) AF: 0.228 AC: 1172 AN: 5150

South Asian (SAS) AF: 0.264 AC: 1272 AN: 4812

European-Finnish (FIN) AF: 0.512 AC: 5417 AN: 10574

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34908 AN: 67960

Other (OTH) AF: 0.458 AC: 968 AN: 2112

Alfa AF: 0.486 Hom.: 63567

Bravo AF: 0.437

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.48
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4357518; hg19: chr1-15080560;