Genetic Variant NM_018029.4:c.136T>A (chr3-73062217-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018029.4(EBLN2):c.136T>A(p.Ser46Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,437,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04184395).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018029.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EBLN2	NM_018029.4	MANE Select	c.136T>A	p.Ser46Thr	missense	Exon 1 of 1	NP_060499.3	Q6P2I7
PPP4R2	NM_174907.4	MANE Select	c.419+1157T>A		intron	N/A	NP_777567.1	Q9NY27-1
PPP4R2	NM_001318026.2		c.305+1157T>A		intron	N/A	NP_001304955.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EBLN2	ENST00000533473.1	TSL:6 MANE Select	c.136T>A	p.Ser46Thr	missense	Exon 1 of 1	ENSP00000432104.1	Q6P2I7
PPP4R2	ENST00000356692.10	TSL:1 MANE Select	c.419+1157T>A		intron	N/A	ENSP00000349124.5	Q9NY27-1
PPP4R2	ENST00000710398.1		c.524+1157T>A		intron	N/A	ENSP00000518252.1	A0AA34QVI2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

218646

AF XY:

0.00

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1437822

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

714286

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32058

American (AMR)

AF:

0.00

AC:

AN:

37714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25452

East Asian (EAS)

AF:

0.00

AC:

AN:

39354

South Asian (SAS)

AF:

0.0000122

AC:

AN:

81844

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52746

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1103454

Other (OTH)

AF:

0.00

AC:

AN:

59482

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.43

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.0026

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.15

M_CAP

Benign

0.0012

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

0.050

REVEL

Benign

0.012

Sift

Benign

0.033

Sift4G

Benign

0.80

Polyphen

0.0

Vest4

0.045

MutPred

0.23

Gain of glycosylation at S49 (P = 0.0062)

MVP

0.067

MPC

0.0048

ClinPred

0.037

GERP RS

-0.46

Varity_R

0.10

gMVP

0.0096

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over