dbSNP rs1354591378: EPPK1:p.Gly2293Gly (chr8-143866375-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.6879C>T(p.Gly2293Gly) 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 0.000041 ( 0 hom., cov: 15)

Exomes 𝑓: 0.000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EPPK1
NM_031308.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.92

Publications

0 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 8-143866375-G-A is Benign according to our data. Variant chr8-143866375-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3035784.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.92 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.6879C>T	p.Gly2293Gly	synonymous	Exon 2 of 2	NP_112598.3	P58107

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EPPK1	ENST00000615648.2	TSL:5 MANE Select	c.6879C>T	p.Gly2293Gly	synonymous	Exon 2 of 2	ENSP00000484472.1	P58107
EPPK1	ENST00000568225.2	TSL:6	c.6804C>T	p.Gly2268Gly	synonymous	Exon 1 of 1	ENSP00000456124.2	A0A075B730
ENSG00000305900	ENST00000813856.1		n.157+12712C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000413

AC:

AN:

121150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000645

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000522

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000243

AC:

AN:

246990

AF XY:

0.0000223

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

753680

Hom.:

Cov.:

AF XY:

0.0000184

AC XY:

AN XY:

381098

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18022

American (AMR)

AF:

0.00

AC:

AN:

19356

Ashkenazi Jewish (ASJ)

AF:

0.0000645

AC:

AN:

15502

East Asian (EAS)

AF:

0.00

AC:

AN:

32426

South Asian (SAS)

AF:

0.00

AC:

AN:

52276

European-Finnish (FIN)

AF:

0.000101

AC:

AN:

29730

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2548

European-Non Finnish (NFE)

AF:

0.0000110

AC:

AN:

547862

Other (OTH)

AF:

0.0000278

AC:

AN:

35958

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000412

AC:

AN:

121258

Hom.:

Cov.:

AF XY:

0.0000348

AC XY:

AN XY:

57526

show subpopulations

African (AFR)

AF:

0.0000643

AC:

AN:

31126

American (AMR)

AF:

0.00

AC:

AN:

12112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3054

East Asian (EAS)

AF:

0.00

AC:

AN:

4080

South Asian (SAS)

AF:

0.00

AC:

AN:

3158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.0000522

AC:

AN:

57498

Other (OTH)

AF:

0.00

AC:

AN:

1522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.00

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

8.3

(source)

DANN

Benign

0.96

PhyloP100

-1.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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