NM_006824.3:c.227C>T

Variant names:

• chr1-43171575-G-A
• rs11559316
• NM_006824.3:c.227C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006824.3(EBNA1BP2):​c.227C>T​(p.Pro76Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P76Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EBNA1BP2 NM_006824.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91
• Publications: 8 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]

MIR6733 (HGNC:50239): (microRNA 6733) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.227C>T	p.Pro76Leu	missense	Exon 3 of 9	NP_006815.2	Q6IB29
	EBNA1BP2	NM_001159936.1		c.392C>T	p.Pro131Leu	missense	Exon 4 of 10	NP_001153408.1	Q99848
	MIR6733	NR_106791.1		n.*77C>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBNA1BP2	ENST00000236051.3	TSL:1 MANE Select	c.227C>T	p.Pro76Leu	missense	Exon 3 of 9	ENSP00000236051.2	Q99848
	EBNA1BP2	ENST00000431635.6	TSL:2	c.392C>T	p.Pro131Leu	missense	Exon 4 of 10	ENSP00000407323.2	H7C2Q8
	EBNA1BP2	ENST00000954564.1		c.227C>T	p.Pro76Leu	missense	Exon 4 of 10	ENSP00000624623.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251424 AF XY: 0.00000736

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.93	P
Vest4		0.47
MutPred		0.66		Loss of disorder (P = 0.0332)
MVP		0.77
MPC		0.36
ClinPred		0.95	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.37
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs11559316; hg19: chr1-43637246;