1-43164644-T-C

Variant names:

• chr1-43164644-T-C
• rs11559312
• NM_006824.3:c.869A>G

Variant summary

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

The NM_006824.3(EBNA1BP2):​c.869A>G​(p.Asn290Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N290I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: EBNA1BP2 NM_006824.3 missense, splice_region
• Scores: Splicing: ADA: 0.9896
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.34

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBNA1BP2	NM_006824.3	c.869A>G	p.Asn290Ser	missense_variant, splice_region_variant	Exon 8 of 9	ENST00000236051.3	NP_006815.2
EBNA1BP2	NM_001159936.1	c.1034A>G	p.Asn345Ser	missense_variant, splice_region_variant	Exon 9 of 10		NP_001153408.1
EBNA1BP2	XM_047441489.1	c.869A>G	p.Asn290Ser	missense_variant, splice_region_variant	Exon 9 of 10		XP_047297445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBNA1BP2	ENST00000236051.3	c.869A>G	p.Asn290Ser	missense_variant, splice_region_variant	Exon 8 of 9	1	NM_006824.3	ENSP00000236051.2
EBNA1BP2	ENST00000431635.6	c.1034A>G	p.Asn345Ser	missense_variant, splice_region_variant	Exon 9 of 10	2		ENSP00000407323.2
EBNA1BP2	ENST00000463906.1	n.788A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251336 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135844

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.14
Sift	Benign	0.22	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.96	.;D
Vest4		0.42
MutPred		0.36		.;Gain of phosphorylation at N290 (P = 0.0023);
MVP		0.61
MPC		0.59
ClinPred		0.69	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.012

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.83
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs11559312; hg19: chr1-43630315;