3-73062217-T-C

Variant names:

• chr3-73062217-T-C
• rs2231924
• NM_018029.4:c.136T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018029.4(EBLN2):​c.136T>C​(p.Ser46Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,589,304 control chromosomes in the GnomAD database, including 213,889 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (22135 hom., cov: 31)
  • Exomes 𝑓: 0.51 (191754 hom.)
• Consequence: EBLN2 NM_018029.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 30 publications found

Genes affected

EBLN2 (HGNC:25493): (endogenous Bornavirus like nucleoprotein 2)

PPP4R2 (HGNC:18296): (protein phosphatase 4 regulatory subunit 2) The protein encoded by this gene is a regulatory subunit of the serine/threonine-protein phosphatase 4 complex. In addition to being required for efficient DNA double strand break repair, this complex plays a role in organization of microtubules at centrosomes and processing of spliceosomal snRNPs. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.131463E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018029.4. 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
	EBLN2	NM_018029.4	MANE Select	c.136T>C	p.Ser46Pro	missense	Exon 1 of 1	NP_060499.3	Q6P2I7
	PPP4R2	NM_174907.4	MANE Select	c.419+1157T>C		intron	N/A	NP_777567.1	Q9NY27-1
	PPP4R2	NM_001318026.2		c.305+1157T>C		intron	N/A	NP_001304955.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBLN2	ENST00000533473.1	TSL:6 MANE Select	c.136T>C	p.Ser46Pro	missense	Exon 1 of 1	ENSP00000432104.1	Q6P2I7
	PPP4R2	ENST00000356692.10	TSL:1 MANE Select	c.419+1157T>C		intron	N/A	ENSP00000349124.5	Q9NY27-1
	PPP4R2	ENST00000710398.1		c.524+1157T>C		intron	N/A	ENSP00000518252.1	A0AA34QVI2

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81297 AN: 151862 Hom.: 22125 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.524

GnomAD2 exomes AF: 0.505 AC: 110340 AN: 218646 AF XY: 0.513

Gnomad AFR exome AF: 0.618

Gnomad AMR exome AF: 0.368

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.423

Gnomad FIN exome AF: 0.488

Gnomad NFE exome AF: 0.510

Gnomad OTH exome AF: 0.506

GnomAD4 exome AF: 0.515 AC: 739751 AN: 1437324 Hom.: 191754 Cov.: 51 AF XY: 0.518 AC XY: 369775 AN XY: 714030

African (AFR) AF: 0.629 AC: 20162 AN: 32042

American (AMR) AF: 0.374 AC: 14088 AN: 37622

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 13080 AN: 25436

East Asian (EAS) AF: 0.418 AC: 16445 AN: 39324

South Asian (SAS) AF: 0.623 AC: 50949 AN: 81790

European-Finnish (FIN) AF: 0.489 AC: 25767 AN: 52730

Middle Eastern (MID) AF: 0.541 AC: 3094 AN: 5718

European-Non Finnish (NFE) AF: 0.512 AC: 564882 AN: 1103190

Other (OTH) AF: 0.526 AC: 31284 AN: 59472

GnomAD4 genome AF: 0.535 AC: 81338 AN: 151980 Hom.: 22135 Cov.: 31 AF XY: 0.531 AC XY: 39430 AN XY: 74284

African (AFR) AF: 0.622 AC: 25764 AN: 41444

American (AMR) AF: 0.434 AC: 6626 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1771 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2250 AN: 5160

South Asian (SAS) AF: 0.619 AC: 2979 AN: 4812

European-Finnish (FIN) AF: 0.483 AC: 5093 AN: 10552

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35202 AN: 67956

Other (OTH) AF: 0.524 AC: 1103 AN: 2106

Alfa AF: 0.531 Hom.: 13043

Bravo AF: 0.528

TwinsUK AF: 0.502 AC: 1863

ALSPAC AF: 0.518 AC: 1995

ESP6500AA AF: 0.626 AC: 2389

ESP6500EA AF: 0.510 AC: 4205

ExAC AF: 0.502 AC: 60473

Asia WGS AF: 0.549 AC: 1909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.28
DANN	Benign	0.45
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.000021	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.012
Sift	Benign	1.0	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.012
MPC		0.0042
ClinPred		0.00058	T
GERP RS		-0.46
Varity_R		0.082
gMVP		0.0040
Mutation Taster		=100/0	polymorphism (auto)

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: rs2231924; hg19: chr3-73111368; COSMIC: COSV55594408; COSMIC: COSV55594408;