chr3-73062217-T-C

Position:

• chr3-73062217-T-C

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBLN2	NM_018029.4	c.136T>C	p.Ser46Pro	missense_variant	1/1	ENST00000533473.1	NP_060499.3
PPP4R2	NM_174907.4	c.419+1157T>C		intron_variant		ENST00000356692.10	NP_777567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBLN2	ENST00000533473.1	c.136T>C	p.Ser46Pro	missense_variant	1/1	6	NM_018029.4	ENSP00000432104.1
PPP4R2	ENST00000356692.10	c.419+1157T>C		intron_variant		1	NM_174907.4	ENSP00000349124.5

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

GnomAD3 exomes AF: 0.505 AC: 110340 AN: 218646 Hom.: 28290 AF XY: 0.513 AC XY: 60763 AN XY: 118430

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 SAS exome AF: 0.625

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

Gnomad4 AFR exome AF: 0.629

Gnomad4 AMR exome AF: 0.374

Gnomad4 ASJ exome AF: 0.514

Gnomad4 EAS exome AF: 0.418

Gnomad4 SAS exome AF: 0.623

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.512

Gnomad4 OTH exome AF: 0.526

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

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.524

Alfa AF: 0.533 Hom.: 9434

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 v4.3

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
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

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

Publications

LitVar

Other links and lift over

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