3-73062330-C-CA

Position:

• chr3-73062330-C-CA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_018029.4(EBLN2):​c.250dup​(p.Arg84LysfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,607,514 control chromosomes in the GnomAD database, including 17,201 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1549 hom., cov: 30)
  • Exomes 𝑓: 0.13 (15652 hom.)
• Consequence: EBLN2 NM_018029.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBLN2	NM_018029.4	c.250dup	p.Arg84LysfsTer18	frameshift_variant	1/1	ENST00000533473.1
PPP4R2	NM_174907.4	c.419+1271dup		intron_variant		ENST00000356692.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBLN2	ENST00000533473.1	c.250dup	p.Arg84LysfsTer18	frameshift_variant	1/1		NM_018029.4	P1
PPP4R2	ENST00000356692.10	c.419+1271dup		intron_variant		1	NM_174907.4	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19605 AN: 152038 Hom.: 1549 Cov.: 30

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.0894

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.128

GnomAD3 exomes AF: 0.148 AC: 34705 AN: 235026 Hom.: 3659 AF XY: 0.155 AC XY: 19834 AN XY: 127562

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0953

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.345

Gnomad SAS exome AF: 0.315

Gnomad FIN exome AF: 0.0832

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.129 AC: 187598 AN: 1455358 Hom.: 15652 Cov.: 62 AF XY: 0.135 AC XY: 98066 AN XY: 723838

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.0902

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.129 AC: 19630 AN: 152156 Hom.: 1549 Cov.: 30 AF XY: 0.132 AC XY: 9829 AN XY: 74362

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.0894

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.131

Alfa AF: 0.131 Hom.: 1044

Bravo AF: 0.125

Asia WGS AF: 0.341 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3832186; hg19: chr3-73111481;