Genetic Variant EPPK1:p.Arg2305Arg (chr8-143866339-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_031308.4(EPPK1):c.6915C>T(p.Arg2305Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 8)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

EPPK1
NM_031308.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.38

Publications

1 publications found

Variant links:

Genes affected

EPPK1 (HGNC:15577): (epiplakin 1) The protein encoded by this gene belongs to the plakin family of proteins, which play a role in the organization of cytoskeletal architecture. This family member is composed of several highly homologous plakin repeats. It may function to maintain the integrity of keratin intermediate filament networks in epithelial cells. Studies of the orthologous mouse protein suggest that it accelerates keratinocyte migration during wound healing. [provided by RefSeq, Oct 2013]

EPPK1 links:

ENSG00000305900 (HGNC:):

ENSG00000305900 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 8-143866339-G-A is Benign according to our data. Variant chr8-143866339-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3052731.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.38 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031308.4. 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
	EPPK1	NM_031308.4	MANE Select	c.6915C>T	p.Arg2305Arg	synonymous	Exon 2 of 2	NP_112598.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EPPK1	ENST00000615648.2	TSL:5 MANE Select	c.6915C>T	p.Arg2305Arg	synonymous	Exon 2 of 2	ENSP00000484472.1
EPPK1	ENST00000568225.2	TSL:6	c.6840C>T	p.Arg2280Arg	synonymous	Exon 1 of 1	ENSP00000456124.2
ENSG00000305900	ENST00000813856.1		n.157+12748C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000349

AC:

AN:

48740

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00114

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000992

Gnomad SAS

AF:

0.00188

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000431

Gnomad OTH

AF:

0.00175

GnomAD2 exomes

AF:

0.0000282

AC:

AN:

248360

AF XY:

0.0000296

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.0000444

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000306

AC:

132

AN:

430856

Hom.:

Cov.:

AF XY:

0.000329

AC XY:

AN XY:

221668

show subpopulations

African (AFR)

AF:

0.0000872

AC:

AN:

11468

American (AMR)

AF:

0.00352

AC:

AN:

12786

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12110

East Asian (EAS)

AF:

0.00140

AC:

AN:

26516

South Asian (SAS)

AF:

0.000350

AC:

AN:

28600

European-Finnish (FIN)

AF:

0.0000397

AC:

AN:

25210

Middle Eastern (MID)

AF:

0.000556

AC:

AN:

1798

European-Non Finnish (NFE)

AF:

0.000108

AC:

AN:

288312

Other (OTH)

AF:

0.000249

AC:

AN:

24056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000348

AC:

AN:

48844

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

AN XY:

22972

show subpopulations

African (AFR)

AF:

0.000360

AC:

AN:

11106

American (AMR)

AF:

0.00114

AC:

AN:

5272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1264

East Asian (EAS)

AF:

0.000998

AC:

AN:

2004

South Asian (SAS)

AF:

0.00189

AC:

AN:

1590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000432

AC:

AN:

23172

Other (OTH)

AF:

0.00169

AC:

AN:

590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000169

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

EPPK1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

9.6

(source)

DANN

Benign

0.95

PhyloP100

-1.4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over