1-43171909-G-T

Position:

• chr1-43171909-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006824.3(EBNA1BP2):​c.127C>A​(p.Pro43Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EBNA1BP2 NM_006824.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19516122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBNA1BP2	NM_006824.3	c.127C>A	p.Pro43Thr	missense_variant	2/9	ENST00000236051.3	NP_006815.2
EBNA1BP2	NM_001159936.1	c.292C>A	p.Pro98Thr	missense_variant	3/10		NP_001153408.1
EBNA1BP2	XM_047441489.1	c.127C>A	p.Pro43Thr	missense_variant	3/10		XP_047297445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBNA1BP2	ENST00000236051.3	c.127C>A	p.Pro43Thr	missense_variant	2/9	1	NM_006824.3	ENSP00000236051.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 22, 2023

The c.292C>A (p.P98T) alteration is located in exon 3 (coding exon 3) of the EBNA1BP2 gene. This alteration results from a C to A substitution at nucleotide position 292, causing the proline (P) at amino acid position 98 to be replaced by a threonine (T). 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	0.074
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.021	T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.034
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.40	.;N
MutationTaster	Benign	0.88	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.025
Sift	Benign	0.17	T;T
Sift4G	Benign	0.37	T;T
Polyphen		0.063	.;B
Vest4		0.37
MutPred		0.35		.;Loss of ubiquitination at K44 (P = 0.046);
MVP		0.45
MPC		0.39
ClinPred		0.34	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.36
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-43637580;