rs854715

Variant names:

• chr1-201284153-A-G
• rs854715
• NM_001005337.3:c.202+249A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-201284153-A-G
• chr1-201284153-A-C
• chr1-201284153-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001005337.3(PKP1):​c.202+249A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 152,304 control chromosomes in the GnomAD database, including 66,811 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.94 (66811 hom., cov: 33)
• Consequence: PKP1 NM_001005337.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35
• Publications: 4 publications found

Genes affected

PKP1 (HGNC:9023): (plakophilin 1) This gene encodes a member of the arm-repeat (armadillo) and plakophilin gene families. Plakophilin proteins contain numerous armadillo repeats, localize to cell desmosomes and nuclei, and participate in linking cadherins to intermediate filaments in the cytoskeleton. This protein may be involved in molecular recruitment and stabilization during desmosome formation. Mutations in this gene have been associated with the ectodermal dysplasia/skin fragility syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

PKP1 Gene-Disease associations (from GenCC):

• epidermolysis bullosa simplex due to plakophilin deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-201284153-A-G is Benign according to our data. Variant chr1-201284153-A-G is described in ClinVar as Benign. ClinVar VariationId is 1272211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005337.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKP1	NM_001005337.3	MANE Select	c.202+249A>G		intron	N/A	NP_001005337.1	Q13835-2
	PKP1	NM_000299.4		c.202+249A>G		intron	N/A	NP_000290.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKP1	ENST00000367324.8	TSL:1 MANE Select	c.202+249A>G		intron	N/A	ENSP00000356293.4	Q13835-2
	PKP1	ENST00000263946.7	TSL:5	c.202+249A>G		intron	N/A	ENSP00000263946.3	Q13835-1
	PKP1	ENST00000352845.3	TSL:5	c.202+249A>G		intron	N/A	ENSP00000295597.3	Q13835-1

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142487 AN: 152186 Hom.: 66764 Cov.: 33

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.963

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.939

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

GnomAD4 genome AF: 0.936 AC: 142591 AN: 152304 Hom.: 66811 Cov.: 33 AF XY: 0.935 AC XY: 69643 AN XY: 74470

African (AFR) AF: 0.898 AC: 37322 AN: 41560

American (AMR) AF: 0.963 AC: 14730 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 3001 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5169 AN: 5170

South Asian (SAS) AF: 0.945 AC: 4560 AN: 4824

European-Finnish (FIN) AF: 0.924 AC: 9823 AN: 10626

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64909 AN: 68032

Other (OTH) AF: 0.939 AC: 1984 AN: 2112

Alfa AF: 0.950 Hom.: 12847

Bravo AF: 0.937

Asia WGS AF: 0.972 AC: 3380 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.67
PhyloP100		-1.4
PromoterAI		-0.12	Neutral
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: rs854715; hg19: chr1-201253281;