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rs2711070

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003628.6(PKP4):c.1909+3322G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,028 control chromosomes in the GnomAD database, including 16,402 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 ( 16402 hom., cov: 33)

Consequence

PKP4
NM_003628.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.230
Variant links:
Genes affected
PKP4 (HGNC:9026): (plakophilin 4) Armadillo-like proteins are characterized by a series of armadillo repeats, first defined in the Drosophila 'armadillo' gene product, that are typically 42 to 45 amino acids in length. These proteins can be divided into subfamilies based on their number of repeats, their overall sequence similarity, and the dispersion of the repeats throughout their sequences. Members of the p120(ctn)/plakophilin subfamily of Armadillo-like proteins, including CTNND1, CTNND2, PKP1, PKP2, PKP4, and ARVCF. PKP4 may be a component of desmosomal plaque and other adhesion plaques and is thought to be involved in regulating junctional plaque organization and cadherin function. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PKP4NM_003628.6 linkuse as main transcriptc.1909+3322G>C intron_variant ENST00000389759.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PKP4ENST00000389759.8 linkuse as main transcriptc.1909+3322G>C intron_variant 1 NM_003628.6 P3Q99569-1

Frequencies

GnomAD3 genomes
AF:
0.446
AC:
67792
AN:
151910
Hom.:
16384
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.259
Gnomad AMI
AF:
0.446
Gnomad AMR
AF:
0.583
Gnomad ASJ
AF:
0.416
Gnomad EAS
AF:
0.597
Gnomad SAS
AF:
0.664
Gnomad FIN
AF:
0.449
Gnomad MID
AF:
0.323
Gnomad NFE
AF:
0.505
Gnomad OTH
AF:
0.437
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.446
AC:
67835
AN:
152028
Hom.:
16402
Cov.:
33
AF XY:
0.450
AC XY:
33425
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.259
Gnomad4 AMR
AF:
0.584
Gnomad4 ASJ
AF:
0.416
Gnomad4 EAS
AF:
0.597
Gnomad4 SAS
AF:
0.665
Gnomad4 FIN
AF:
0.449
Gnomad4 NFE
AF:
0.505
Gnomad4 OTH
AF:
0.438
Alfa
AF:
0.478
Hom.:
2249
Bravo
AF:
0.445
Asia WGS
AF:
0.585
AC:
2032
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
Cadd
Benign
2.0
Dann
Benign
0.57

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2711070; hg19: chr2-159502533; API