Genetic Variant EBLN2:p.Ser46Pro (chr3-73062217-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018029.4(EBLN2):c.136T>C(p.Ser46Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,589,304 control chromosomes in the GnomAD database, including 213,889 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.54 ( 22135 hom., cov: 31)

Exomes 𝑓: 0.51 ( 191754 hom. )

Consequence

EBLN2
NM_018029.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.03

Publications

30 publications found

Variant links:

Genes affected

EBLN2 (HGNC:25493): (endogenous Bornavirus like nucleoprotein 2)

EBLN2 links:

PPP4R2 (HGNC:18296): (protein phosphatase 4 regulatory subunit 2) The protein encoded by this gene is a regulatory subunit of the serine/threonine-protein phosphatase 4 complex. In addition to being required for efficient DNA double strand break repair, this complex plays a role in organization of microtubules at centrosomes and processing of spliceosomal snRNPs. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

PPP4R2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.131463E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBLN2	NM_018029.4 link	c.136T>C	p.Ser46Pro	missense_variant	Exon 1 of 1	ENST00000533473.1	NP_060499.3	Q6P2I7
PPP4R2	NM_174907.4 link	c.419+1157T>C		intron_variant	Intron 5 of 8	ENST00000356692.10	NP_777567.1	Q9NY27-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBLN2	ENST00000533473.1 link	c.136T>C	p.Ser46Pro	missense_variant	Exon 1 of 1	6	NM_018029.4	ENSP00000432104.1		Q6P2I7
PPP4R2	ENST00000356692.10 link	c.419+1157T>C		intron_variant	Intron 5 of 8	1	NM_174907.4	ENSP00000349124.5		Q9NY27-1

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

81297

AN:

151862

Hom.:

22125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.622

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.437

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.483

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.518

Gnomad OTH

AF:

0.524

GnomAD2 exomes

AF:

0.505

AC:

110340

AN:

218646

AF XY:

0.513

show subpopulations

Gnomad AFR exome

AF:

0.618

Gnomad AMR exome

AF:

0.368

Gnomad ASJ exome

AF:

0.517

Gnomad EAS exome

AF:

0.423

Gnomad FIN exome

AF:

0.488

Gnomad NFE exome

AF:

0.510

Gnomad OTH exome

AF:

0.506

GnomAD4 exome

AF:

0.515

AC:

739751

AN:

1437324

Hom.:

191754

Cov.:

AF XY:

0.518

AC XY:

369775

AN XY:

714030

show subpopulations

African (AFR)

AF:

0.629

AC:

20162

AN:

32042

American (AMR)

AF:

0.374

AC:

14088

AN:

37622

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

13080

AN:

25436

East Asian (EAS)

AF:

0.418

AC:

16445

AN:

39324

South Asian (SAS)

AF:

0.623

AC:

50949

AN:

81790

European-Finnish (FIN)

AF:

0.489

AC:

25767

AN:

52730

Middle Eastern (MID)

AF:

0.541

AC:

3094

AN:

5718

European-Non Finnish (NFE)

AF:

0.512

AC:

564882

AN:

1103190

Other (OTH)

AF:

0.526

AC:

31284

AN:

59472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

19422

38844

58265

77687

97109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16484

32968

49452

65936

82420

<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:

0.535

AC:

81338

AN:

151980

Hom.:

22135

Cov.:

AF XY:

0.531

AC XY:

39430

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.622

AC:

25764

AN:

41444

American (AMR)

AF:

0.434

AC:

6626

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

1771

AN:

3468

East Asian (EAS)

AF:

0.436

AC:

2250

AN:

5160

South Asian (SAS)

AF:

0.619

AC:

2979

AN:

4812

European-Finnish (FIN)

AF:

0.483

AC:

5093

AN:

10552

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.518

AC:

35202

AN:

67956

Other (OTH)

AF:

0.524

AC:

1103

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1916

3832

5748

7664

9580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<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:

0.531

Hom.:

13043

Bravo

AF:

0.528

TwinsUK

AF:

0.502

AC:

1863

ALSPAC

AF:

0.518

AC:

1995

ESP6500AA

AF:

0.626

AC:

2389

ESP6500EA

AF:

0.510

AC:

4205

ExAC

AF:

0.502

AC:

60473

Asia WGS

AF:

0.549

AC:

1909

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.28

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.0011

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.14

MetaRNN

Benign

0.000021

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

PhyloP100

-1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

1.7

REVEL

Benign

0.012

Sift

Benign

1.0

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.012

MPC

0.0042

ClinPred

0.00058

GERP RS

-0.46

Varity_R

0.082

gMVP

0.0040

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over