rs1014455707

Variant names:

• chr1-43170828-C-A
• rs1014455707
• NM_006824.3:c.375G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006824.3(EBNA1BP2):​c.375G>T​(p.Gln125His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,788 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EBNA1BP2 NM_006824.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.39
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30126703).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBNA1BP2	NM_006824.3	MANE Select	c.375G>T	p.Gln125His	missense	Exon 4 of 9	NP_006815.2	Q6IB29
	EBNA1BP2	NM_001159936.1		c.540G>T	p.Gln180His	missense	Exon 5 of 10	NP_001153408.1	Q99848

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBNA1BP2	ENST00000236051.3	TSL:1 MANE Select	c.375G>T	p.Gln125His	missense	Exon 4 of 9	ENSP00000236051.2	Q99848
	EBNA1BP2	ENST00000431635.6	TSL:2	c.540G>T	p.Gln180His	missense	Exon 5 of 10	ENSP00000407323.2	H7C2Q8
	EBNA1BP2	ENST00000954564.1		c.375G>T	p.Gln125His	missense	Exon 5 of 10	ENSP00000624623.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000414 AC: 1 AN: 241492 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000904

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452788 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722636

African (AFR) AF: 0.00 AC: 0 AN: 32896

American (AMR) AF: 0.00 AC: 0 AN: 43090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25968

East Asian (EAS) AF: 0.00 AC: 0 AN: 38986

South Asian (SAS) AF: 0.00 AC: 0 AN: 84406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108378

Other (OTH) AF: 0.00 AC: 0 AN: 60010

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.4
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.23
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.022	D
Polyphen		1.0	D
Vest4		0.24
MutPred		0.45		Gain of methylation at R122 (P = 0.0415)
MVP		0.72
MPC		0.32
ClinPred		0.67	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.62
gMVP		0.13
Mutation Taster		=46/54	disease causing

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

Other links and lift over

dbSNP: rs1014455707; hg19: chr1-43636499;