1-43171575-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006824.3(EBNA1BP2):c.227C>G(p.Pro76Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00753 in 1,614,084 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P76Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0073 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 70 hom. )

Consequence

EBNA1BP2
NM_006824.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.91

Publications

8 publications found

Variant links:

Genes affected

EBNA1BP2 (HGNC:15531): (EBNA1 binding protein 2) Enables RNA binding activity. Predicted to be involved in rRNA processing and ribosomal large subunit biogenesis. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

EBNA1BP2 links:

MIR6733 (HGNC:50239): (microRNA 6733) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6733 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009445906).

BP6

Variant 1-43171575-G-C is Benign according to our data. Variant chr1-43171575-G-C is described in ClinVar as Benign. ClinVar VariationId is 777906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 10 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006824.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EBNA1BP2	NM_006824.3	MANE Select	c.227C>G	p.Pro76Arg	missense	Exon 3 of 9	NP_006815.2	Q6IB29
EBNA1BP2	NM_001159936.1		c.392C>G	p.Pro131Arg	missense	Exon 4 of 10	NP_001153408.1	Q99848
MIR6733	NR_106791.1		n.*77C>G		downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EBNA1BP2	ENST00000236051.3	TSL:1 MANE Select	c.227C>G	p.Pro76Arg	missense	Exon 3 of 9	ENSP00000236051.2	Q99848
EBNA1BP2	ENST00000431635.6	TSL:2	c.392C>G	p.Pro131Arg	missense	Exon 4 of 10	ENSP00000407323.2	H7C2Q8
EBNA1BP2	ENST00000954564.1		c.227C>G	p.Pro76Arg	missense	Exon 4 of 10	ENSP00000624623.1

Frequencies

GnomAD3 genomes

AF:

0.00732

AC:

1113

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.0245

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00652

AC:

1640

AN:

251424

AF XY:

0.00620

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0197

Gnomad NFE exome

AF:

0.00862

Gnomad OTH exome

AF:

0.00733

GnomAD4 exome

AF:

0.00756

AC:

11045

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

5406

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33478

American (AMR)

AF:

0.00143

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00157

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00378

AC:

326

AN:

86254

European-Finnish (FIN)

AF:

0.0181

AC:

969

AN:

53418

Middle Eastern (MID)

AF:

0.00641

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00822

AC:

9143

AN:

1112004

Other (OTH)

AF:

0.00709

AC:

428

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

683

1366

2048

2731

3414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

312

624

936

1248

1560

<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:

0.00731

AC:

1113

AN:

152218

Hom.:

Cov.:

AF XY:

0.00802

AC XY:

597

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.00166

AC:

AN:

41540

American (AMR)

AF:

0.00177

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00332

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0245

AC:

259

AN:

10584

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0107

AC:

730

AN:

68016

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

109

164

218

273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00992

Hom.:

Bravo

AF:

0.00465

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.00633

AC:

768

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00883

EpiControl

AF:

0.00705

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0094

MetaSVM

Benign

-0.61

MutationAssessor

Pathogenic

3.2

PhyloP100

3.9

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-7.0

REVEL

Uncertain

0.33

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.48

MVP

0.76

MPC

0.63

ClinPred

0.098

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.73

gMVP

0.33

Mutation Taster

=73/27

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over