Genetic Variant NM_006824.3:c.452G>A (chr1-43169024-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006824.3(EBNA1BP2):c.452G>A(p.Arg151Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

EBNA1BP2
NM_006824.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.26

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBNA1BP2	NM_006824.3 link	c.452G>A	p.Arg151Gln	missense_variant	Exon 5 of 9	ENST00000236051.3	NP_006815.2	Q99848Q6IB29
EBNA1BP2	NM_001159936.1 link	c.617G>A	p.Arg206Gln	missense_variant	Exon 6 of 10		NP_001153408.1	Q99848H7C2Q8
EBNA1BP2	XM_047441489.1 link	c.452G>A	p.Arg151Gln	missense_variant	Exon 6 of 10		XP_047297445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EBNA1BP2	ENST00000236051.3 link	c.452G>A	p.Arg151Gln	missense_variant	Exon 5 of 9	1	NM_006824.3	ENSP00000236051.2	Q99848
EBNA1BP2	ENST00000431635.6 link	c.617G>A	p.Arg206Gln	missense_variant	Exon 6 of 10	2		ENSP00000407323.2	H7C2Q8
EBNA1BP2	ENST00000463906.1 link	n.371G>A		non_coding_transcript_exon_variant	Exon 2 of 6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.617G>A (p.R206Q) alteration is located in exon 6 (coding exon 6) of the EBNA1BP2 gene. This alteration results from a G to A substitution at nucleotide position 617, causing the arginine (R) at amino acid position 206 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

T;T

Eigen

Pathogenic

0.98

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.068

MetaRNN

Pathogenic

0.85

D;D

MetaSVM

Uncertain

0.00090

MutationAssessor

Uncertain

2.6

.;M

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

1.0

.;D

Vest4

0.83

MutPred

0.58

.;Gain of ubiquitination at K149 (P = 0.026);

MVP

0.98

MPC

0.97

ClinPred

1.0

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.77

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over