1-43164487-G-A

Position:

• chr1-43164487-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006824.3(EBNA1BP2):​c.877C>T​(p.Pro293Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 5.90

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34770113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBNA1BP2	NM_006824.3	c.877C>T	p.Pro293Ser	missense_variant	9/9	ENST00000236051.3	NP_006815.2
EBNA1BP2	NM_001159936.1	c.1042C>T	p.Pro348Ser	missense_variant	10/10		NP_001153408.1
EBNA1BP2	XM_047441489.1	c.877C>T	p.Pro293Ser	missense_variant	10/10		XP_047297445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBNA1BP2	ENST00000236051.3	c.877C>T	p.Pro293Ser	missense_variant	9/9	1	NM_006824.3	ENSP00000236051	P1
EBNA1BP2	ENST00000431635.6	c.1042C>T	p.Pro348Ser	missense_variant	10/10	2		ENSP00000407323
EBNA1BP2	ENST00000463906.1	n.796C>T		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Apr 22, 2022

The c.1042C>T (p.P348S) alteration is located in exon 10 (coding exon 10) of the EBNA1BP2 gene. This alteration results from a C to T substitution at nucleotide position 1042, causing the proline (P) at amino acid position 348 to be replaced by a serine (S). 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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.0	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Uncertain	0.34
Sift	Benign	0.031	D;D
Sift4G	Benign	0.28	T;T
Polyphen		1.0	.;D
Vest4		0.42
MutPred		0.48		.;Gain of phosphorylation at P293 (P = 0.0013);
MVP		0.79
MPC		1.1
ClinPred		0.99	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.052

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr1-43630158;